A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)
A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
Individual members of North American ethnic groups with ancient historic ancestral origins in Asia.
Established cell cultures that have the potential to propagate indefinitely.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)
Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.

Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. (1/67)

Pathogenic alpha-synuclein (alphaS) gene mutations occur in rare familial Parkinson's disease (PD) kindreds, and wild-type alphaS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease, but beta-synuclein (betaS) and gamma-synuclein (gammaS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to alphaS and betaS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to gammaS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the alphaS- and betaS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative "synucleinopathies" by implicating betaS and gammaS, in addition to alphaS, in the onset/progression of PD and DLB.  (+info)

Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. (2/67)

alpha-, beta-, and gamma-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because alpha-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the synucleins are still unknown. For this reason, we characterized alpha-, beta-, and gamma-synuclein expression in primary hippocampal neuronal cultures and showed that the onset of alpha- and beta-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formation. In mature cultured primary neurons, alpha- and beta-synuclein colocalized almost exclusively with synaptophysin in the presynaptic terminal, whereas little gamma-synuclein was expressed at all. To assess the function of alpha-synuclein, we suppressed expression of this protein with antisense oligonucleotide technology. Morphometric ultrastructural analysis of the alpha-synuclein antisense oligonucleotide-treated cultures revealed a significant reduction in the distal pool of synaptic vesicles. These data suggest that one function of alpha-synuclein may be to regulate the size of distinct pools of synaptic vesicles in mature neurons.  (+info)

Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. (3/67)

Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of alpha-synuclein (alphaS) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients. Further, beta-synuclein (betaS) and gamma-synuclein (gammaS) immunoreactivity was detected in spheroids but not in LB-like or glial inclusions. Western blot analysis demonstrated high-molecular weight alphaS aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of alphaS were markedly reduced in the Triton X-100-soluble fractions compared to control brain, and unlike other synucleinopathies, insoluble alphaS did not accumulate in the formic acid-soluble fraction. These findings expand the concept of neurodegenerative synucleinopathies by implicating alphaS, betaS, and gammaS in the pathogenesis of NBIA 1.  (+info)

Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed its homologs. (4/67)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies. Recently, two point mutations in alpha-synuclein were found to be associated with familial PD, but as of yet no mutations have been described in the homologous genes beta- and gamma-synuclein. alpha-Synuclein forms the major fibrillar component of Lewy bodies, but these do not stain for beta- or gamma-synuclein. This result is very surprising, given the extent of sequence conservation and the high similarity in expression and subcellular localization, in particular between alpha- and beta-synuclein. Here we compare in vitro fibrillogenesis of all three purified synucleins. We show that fresh solutions of alpha-, beta-, and gamma- synuclein show the same natively unfolded structure. While over time alpha-synuclein forms the previously described fibrils, no fibrils could be detected for beta- and gamma-synuclein under the same conditions. Most importantly, beta- and gamma-synuclein could not be cross-seeded with alpha-synuclein fibrils. However, under conditions that drastically accelerate aggregation, gamma-synuclein can form fibrils with a lag phase roughly three times longer than alpha-synuclein. These results indicate that beta- and gamma-synuclein are intrinsically less fibrillogenic than alpha-synuclein and cannot form mixed fibrils with alpha-synuclein, which may explain why they do not appear in the pathological hallmarks of PD, although they are closely related to alpha-synuclein and are also abundant in brain.  (+info)

A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. (5/67)

Neuronal and oligodendrocytic aggregates of fibrillar alpha-synuclein define several diseases of the nervous system. It is likely that these inclusions impair vital metabolic processes and compromise viability of affected cells. Here, we report that a 12-amino acid stretch ((71)VTGVTAVAQKTV(82)) in the middle of the hydrophobic domain of human alpha-synuclein is necessary and sufficient for its fibrillization based on the following observations: 1) human beta-synuclein is highly homologous to alpha-synuclein but lacks these 12 residues, and it does not assemble into filaments in vitro; 2) the rate of alpha-synuclein polymerization in vitro decreases after the introduction of a single charged amino acid within these 12 residues, and a deletion within this region abrogates assembly; 3) this stretch of 12 amino acids appears to form the core of alpha-synuclein filaments, because it is resistant to proteolytic digestion in alpha-synuclein filaments; and 4) synthetic peptides corresponding to this 12-amino acid stretch self-polymerize to form filaments, and these peptides promote fibrillization of full-length human alpha-synuclein in vitro. Thus, we have identified key sequence elements necessary for the assembly of human alpha-synuclein into filaments, and these elements may be exploited as targets for the design of drugs that inhibit alpha-synuclein fibrillization and might arrest disease progression.  (+info)

Chicken synucleins: cloning and expression in the developing embryo. (6/67)

Synucleins comprise a family of small intracellular proteins that have recently attracted considerable attention because of their involvement in human diseases. Mutations of alpha-synuclein has been found in several families with hereditary early-onset Parkinson's disease and accumulation of this protein in characteristic cytoplasmic inclusions is a pathohistological hallmark of several neurodegenerative diseases that have been recently classified as 'alpha;-synucleinopathies' (reviewed in Brain Res. Bull. 50 (1999) 465; J. Neurosci. Res. 58 (1999) 120; Philos. Trans. R. Soc. Lond. Biol. Sci. 354 (1999) 1101; Brain Pathol. 9 (1999) 733). Aggregates of beta-synuclein and persyn (gamma-synuclein) also have been found in dystrophic neurites associated with Parkinson's and other neurodegenerative diseases (Proc. Natl. Acad. Sci. USA 96 (1999) 13450; and our unpublished observations). Moreover, persyn has been implicated in malignization of breast tumours (Cancer Res. 57 (1997) 759; Cancer Res. 59 (1999) 742; Hum. Mol. Genet. 7 (1998) 1417). All synucleins have distinct, although overlapping, patterns of expression in the embryonic, postnatal and adult mammalian nervous systems, suggesting important, although still not clear, biological functions in neuronal developing. Chicken embryo is a unique object for developmental studies that allows in vivo manipulations not always possible for mammalian embryos. Studies of synucleins expression in this model system could shed light on their functions in the developing nervous system. We cloned three chicken synucleins from the embryonic neural cDNA libraries and studied their expression in normal chicken embryonic tissues by Northern and in situ hybridization with specific probes. Our results demonstrate that primary structures and expression patterns of synucleins are similar in birds and mammals, suggesting that conserved function of synucleins is important for embryonic development of vertebrates.  (+info)

Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization. (7/67)

alpha-Synuclein is a protein normally involved in presynaptic vesicle homeostasis. It participates in the development of Parkinson's disease, in which the nerve cell lesions, Lewy bodies, accumulate alpha-synuclein filaments. The synaptic neurotransmitter release is primarily dependent on Ca(2+)-regulated processes. A microdialysis technique was applied showing that alpha-synuclein binds Ca(2+) with an IC(50) of about 2-300 microm and in a reaction uninhibited by a 50-fold excess of Mg(2+). The Ca(2+)-binding site consists of a novel C-terminally localized acidic 32-amino acid domain also present in the homologue beta-synuclein, as shown by Ca(2+) binding to truncated recombinant and synthetic alpha-synuclein peptides. Ca(2+) binding affects the functional properties of alpha-synuclein. First, the ligand binding of (125)I-labeled bovine microtubule-associated protein 1A is stimulated by Ca(2+) ions in the 1-500 microm range and is dependent on an intact Ca(2+) binding site in alpha-synuclein. Second, the Ca(2+) binding stimulates the proportion of (125)I-alpha-synuclein-containing oligomers. This suggests that Ca(2+) ions may both participate in normal alpha-synuclein functions in the nerve terminal and exercise pathological effects involved in the formation of Lewy bodies.  (+info)

Induction of alpha-synuclein aggregation by intracellular nitrative insult. (8/67)

Brain lesions containing filamentous and aggregated alpha-synuclein are hallmarks of neurodegenerative synucleinopathies. Oxidative stress has been implicated in the formation of these lesions. Using HEK 293 cells stably transfected with wild-type and mutant alpha-synuclein, we demonstrated that intracellular generation of nitrating agents results in the formation of alpha-synuclein aggregates. Cells were exposed simultaneously to nitric oxide- and superoxide-generating compounds, and the intracellular formation of peroxynitrite was demonstrated by monitoring the oxidation of dihydrorhodamine 123 and the nitration of alpha-synuclein. Light microscopy using antibodies against alpha-synuclein and electron microscopy revealed the presence of perinuclear aggregates under conditions in which peroxynitrite was generated but not when cells were exposed to nitric oxide- or superoxide-generating compounds separately. alpha-Synuclein aggregates were observed in 20-30% of cells expressing wild-type or A53T mutant alpha-synuclein and in 5% of cells expressing A30P mutant alpha-synuclein. No evidence of synuclein aggregation was observed in untransfected cells or cells expressing beta-synuclein. In contrast, selective inhibition of the proteasome resulted in the formation of aggregates detected with antibodies to ubiquitin in the majority of the untransfected cells and cells expressing alpha-synuclein. However, alpha-synuclein did not colocalize with these aggregates, indicating that inhibition of the proteasome does not promote alpha-synuclein aggregation. In addition, proteasome inhibition did not alter the steady-state levels of alpha-synuclein, but addition of the lysosomotropic agent ammonium chloride significantly increased the amount of alpha-synuclein, indicating that lysosomes are involved in degradation of alpha-synuclein. Our data indicate that nitrative and oxidative insult may initiate pathogenesis of alpha-synuclein aggregates.  (+info)

Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimers disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016 ...
After graduation from the University of Graz in 1985 he spent several years heading a neurobiology group at the University with research in the field of brain metabolism and animal model development after which he was involved for many years in University and industrial research programs in Europe, North America and Asia. He established a global network of research collaborations and stimulated intensive scientific information exchange. Besides his involvement in research on neurotrophic and neuroprotective factors, he spearheaded several international clinical studies in Alzheimers disease, vascular dementia and ischemic stroke from 1989 onwards. When he founded his first CRO, JSW-Lifesciences 1999, the research activities are concentrated on the role of alpha and beta-synuclein in pathogenesis of PD and AD, to explore new therapeutic possibilities. He created and standardized improved transgenic and induced rodent models of neurodegenerative diseases. He gained enormous experience in use of ...
A team of scientists from Japan and the University of California, San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein promote neurodegeneration.
Mutations in genes known as SNCA and SNCB can cause dementia with Lewy bodies. The SNCA and SNCB genes provide instructions for making proteins, called alpha-synuclein and beta-synuclein, respectively, that are found primarily in the brain. Alpha-synuclein plays a role in communication between nerve cells (neurons), helping to regulate the release of chemical messengers (neurotransmitters). Beta-synuclein is likely involved in a process that allows neurons to change and adapt over time, which is necessary for learning and memory. Beta-synuclein may also prevent harmful accumulation of alpha-synuclein in neurons.. Mutations in another gene called GBA or a certain version of a gene called APOE increase the risk of developing the condition, but are not a direct cause. The enzyme produced from the GBA gene is found throughout the body in cell structures called lysosomes that digest and recycle proteins and other materials that are no longer needed. The APOE gene provides instructions for making a ...
Parkinsons disease is a progressive neurodegenerative disorder of the central nervous system that affects one in 100 people over age 60, and after Alzheimers disease is the second most common neurodegenerative disorder. There are an estimated 7 million to 10 million patients living with Parkinsons disease worldwide.. Synucleins are a family of proteins, of which there are three known members: α-synuclein, β-synuclein, and ɣ-synuclein. The α- and β-synuclein proteins are found primarily in brain tissue. The ɣ-synuclein protein is found primarily in the peripheral nervous system and retina, as well as several tumor types. While the role synuclein proteins play in normal cellular functioning has not been fully determined, there are data to suggest that synucleins assist with the stability of cellular membranes and/or their turnover.. Mutations and changes in the levels of α-synuclein have been associated with multiple neurodegenerative illnesses, including Parkinsons disease. This ...
Synucleins: A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.
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The new method from the researchers at Chalmers University of Technology makes it possible to study tiny quantities of biological molecules without using fluorescent markers. This is a great advantage when tracking natural reactions, since the markers often affect the reactions you want to observe, especially when working with small proteins such as α-synuclein.. The chemical differences between the two lipids used are very small, but still we observed dramatic differences in how α-synuclein affected the different vesicles, says Pernilla Wittung-Stafshede.. We believe that lipid chemistry is not the only determining factor, but also that there are macroscopic differences between the two membranes - such as the dynamics and interactions between the lipids. No one has really looked closely at what happens to the membrane itself when α-synuclein binds to it, and never at these low concentrations.. The next step for the researchers is to investigate variants of the α-synuclein protein with ...
Synucleins represent a conserved family of small proteins that include α-, β-, and γ- isoforms, which are highly expressed in neurons of the vertebrate nervous system. The normal function of these proteins is not well ...
Synucleinopathies, a group of neurodegenerative diseases, are characterized by the pathological deposition of aggregates of the misfolded α-synuclein protein.
Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in ...
The study found that a structural core within a toxic tangle of alpha-synuclein protein molecules allows it to insert itself into the wall of a neuron.
Insoluble and fibrillar forms of α-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. α-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. α-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for α-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuinss role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to
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January 25, 2017. Parkinsons disease (PD) and other synucleinopathies are known to be linked to the misfolding of alpha-synuclein protein in neurons. Less clear is how this misfolding relates to the growing number of genes implicated in PD through analysis of human genetics. Two new studies from researchers affiliated with Whitehead Institute and Massachusetts Institute of Technology explain how they used a suite of novel biological and computational methods to shed light on the question.. ...
Title:A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies. VOLUME: 19 ISSUE: 6. Author(s):Larisa Ryskalin, Carla L. Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella and Francesco Fornai*. Affiliation:Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia. Keywords:Alpha synuclein, synucleinopathies, alpha synuclein aggregates, loss-of-function, co-chaperonine, neurodegeneration, neuroprotection.. Abstract:Alpha synuclein (α-syn) belongs to a class of proteins which ...
I studied the effects of a targeted inactivation of the γ-synuclein gene on murine physiology and development, later extending these studies to include α-synuclein and α/γ-synuclein null mutant mice which I produced. All these animals are viable and fertile with no gross physiological of morphological abnormalities. A quantitative evaluation of neuronal populations within the midbrain showed a reduction in the number of depamergic neurons in the SNpc region but not in ventral tegmental area (VTA) of adult γ-synuclein null mutant mice. Similar reductions were revealed in α-synuclein and double α/γ-synuclein null mutant animals. However, in none of these mutants did this lead to significant changes in levels of striatal dopamine or dopamine metabolite levels or motor function. No similar changes were observed in peripheral sensory ganglia. In all three studied types of null mutants, dopaminergic neurons of SNpc were resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. ...
Accumulation of the α-synuclein (α-syn) protein is a hallmark of a group of brain disorders collectively known as synucleinopathies. The mechanisms responsible for α-syn accumulation are not well understood. Several studies suggest a link between synucleinopathies and the cholesterol metabolite 27-hydroxycholesterol (27-OHC). 27-OHC is the major cholesterol metabolite in the blood that crosses the blood brain barrier, and its levels can increase following hypercholesterolemia, aging, and oxidative stress, which are all factors for increased synucleinopathy risk. In this study, we determined the extent to which 27-OHC regulates α-syn levels in human dopaminergic neurons, the cell type in which α-syn accumulates in PD, a major synucleinopathy disorder. Our results show that 27-OHC significantly increases the protein levels, not the mRNA expression of α-syn. The effects of 27-OHC appear to be independent of an action through liver X receptors (LXR), its cognate receptors, as the LXR agonist, GW3965,
Dr. El-Agnaf is considered a pioneer in the field of Parkinsons disease and related disorders. In 1998, Dr El-Agnaf demonstrated for the first time that mutations in α-synuclein protein associated with familial cases of Parkinsons disease increased the tendency of the α-synuclein to aggregate and form amyloid-like fibrils compared to the wild-type protein. Several inventions have emerged from his research, including the unexpected discovery that neuronal cells constitutively release α-synuclein protein into the culture medium, and α-synuclein is normally present in human CSF and peripheral plasma. His discoveries have greatly impacted the scientific research community, provided further insight into the molecular pathogenesis of Parkinsons disease, and offered new opportunities for the development of novel diagnostic and therapeutic tools for Parkinsons disease. His research has also been translated into clinical studies to evaluate the potential use of α-synuclein in body fluids as ...
alpha Synuclein antibody [4D6] (synuclein, alpha (non A4 component of amyloid precursor)) for ELISA, IHC, IHC-Fr, IHC-P, WB. Anti-alpha Synuclein mAb (GTX21903) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
alpha Synuclein (phospho Ser129) antibody (synuclein, alpha (non A4 component of amyloid precursor)) for ICC/IF, IHC-P, WB. Anti-alpha Synuclein (phospho Ser129) pAb (GTX54991) is tested in Human, Mouse samples. 100% Ab-Assurance.
TY - JOUR. T1 - Exploring the accessible conformations of N-terminal acetylated α-synuclein. AU - Moriarty, Gina M.. AU - Janowska, Maria K.. AU - Kang, Lijuan. AU - Baum, Jean. PY - 2013/4/17. Y1 - 2013/4/17. N2 - Abstract Alpha synuclein (αsyn) fibrils are found in the Lewy Bodies of patients with Parkinsons disease (PD). The aggregation of the αsyn monomer to soluble oligomers and insoluble fibril aggregates is believed to be one of the causes of PD. Recently, the view of the native state of αsyn as a monomeric ensemble was challenged by a report suggesting that αsyn exists in its native state as a helical tetramer. This review reports on our current understanding of αsyn within the context of these recent developments and describes the work performed by a number of groups to address the monomer/tetramer debate. A number of in depth studies have subsequently shown that both non-acetylated and acetylated αsyn purified under mild conditions are primarily monomer. A description of the ...
Anti-Alpha synuclein antibody, AS08 358, P37840α-synuclein is normally an unstructured soluble protein that can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinsons disease,dementia with Lew
Overall, our data support the notion that aggregation of α-synuclein is a central element of its neurotoxicity, extending results from previous studies showing that PD mutants of α-synuclein increase the propensity of protofibril or fibril formation of α-synuclein (Narhi et al., 1999; Conway et al., 2000; Greenbaum et al., 2005; Ono et al., 2011) and thus pathology in familial PD cases (Polymeropoulos et al., 1997; Krüger et al., 1998; Zarranz et al., 2004). Mechanistically, α-synuclein aggregation could cause neurotoxicity via at least two pathways. Aggregation of α-synuclein could be in itself neurotoxic. The resulting aggregates could damage neurons either as oligomers or as inclusion bodies, thereby impairing neuronal viability (Spillantini and Goedert, 2000; Masliah et al., 2001; Kayed et al., 2003; Volles and Lansbury, 2003; Lindersson et al., 2004; Lansbury and Lashuel, 2006; Tsika et al., 2010; Colla et al., 2012). Alternatively, α-synuclein aggregates could serve to nucleate ...
Meanwhile, at the second biannual Advances in Alzheimers and Parkinsons Therapies Focus Meeting (AAT-AD/PD), held virtually April 2 to 5, researchers from Roche presented baseline data from this trial, as well as data suggesting that exploratory digital measures collected by smartphones may indeed be useful. Immunotherapy approaches remain popular, with AC Immune researchers at the conference describing an antibody candidate about to enter the clinic.. Because misfolded α-synuclein is believed to spread from cell to cell, numerous groups are targeting this extracellular form of the normally intraneuronal protein with antibodies. Biogens antibody BIIB054 is in Phase 2 but the company did not present at AAT-AD/PD (May 2018 conference news). Other candidates, such as AbbVies ABBV-0805 and AstraZenecas MEDI1341, remain in Phase 1.. Roche/Prothenas prasinezumab is the furthest along clinically. It selectively recognizes aggregated α-synuclein over monomeric forms. Phase 1 data showed that it ...
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Rabbit recombinant monoclonal alpha + beta Synuclein antibody [EP1646Y] validated for WB, Flow Cyt, ICC/IF and tested in Human, Mouse and Rat. Referenced in 10…
Rabbit polyclonal alpha Synuclein (phospho Y125) antibody validated for WB, ICC/IF and tested in Human. Immunogen corresponding to synthetic peptide
Dr. Amberley Stephens joined the group in 2014 while finishing her PhD in molecular microbiology at the University of Nottingham. The main topic of her research is studying α-synuclein under different environmental conditions and how these effect the monomer state and aggregation of the protein. Of particular interest is the interaction of α-synuclein with divalent cations and synaptic vesicles, leading us to investigate potential mechanisms for α-synuclein switching from a physiological function to pathological aggregation.. ...
Detect and quantitate human Alpha-synuclein in biological fluids such as serum, plasma, cerebrospinal fluid and cell culture supernatants using a homogeneous AlphaLISA no-wash assay.
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
Lee and colleagues found that injecting preformed clumps of human alpha-synuclein into the brains of young mice accelerated disease onset and severity. These clumps seemed to act as seeds that recruited even the mouse version of alpha-synuclein into new clumps, which then spread throughout the brain. The pattern of spreading from neuron to neuron suggests that the clumps may hijack the highway traveled by normal brain signals ...
Dr. El-Agnaf is considered a pioneer in the field of Parkinsons disease and related disorders. In 1998, Dr El-Agnaf demonstrated for the first time that mutations in α-synuclein protein associated with familial cases of Parkinsons disease increased the tendency of the α-synuclein to aggregate and form amyloid-like fibrils compared to the wild-type protein. Several inventions have emerged from his research, including the unexpected discovery that neuronal cells constitutively release α-synuclein protein into the culture medium, and α-synuclein is normally present in human CSF and peripheral plasma. His discoveries have greatly impacted the scientific research community, provided further insight into the molecular pathogenesis of Parkinsons disease, and offered new opportunities for the development of novel diagnostic and therapeutic tools for Parkinsons disease. His research has also been translated into clinical studies to evaluate the potential use of α-synuclein in body fluids as ...
Parkinsons disease is a movement disorder characterized by nigrostriatal dopamine pathway degeneration and neuronal α-synuclein accumulation. Pathogenesis is associated with mutations in α-synuclein and Gba1 encoding alleles. Animal models created to date do not recapitulate the spectrum of clinical disease features. This thesis characterizes the bi-genic Synergy mouse, hypothesized to demonstrate motor behavioural and histological abnormalities downstream of α-synuclein overexpression and mutated Gba1. Synergy and SNCA mice (overexpressed α-synuclein with wild-type Gba1) have early onset deficits in motor coordination, muscle strength and nest building. Both exhibit increased α-synuclein concentration in the brain and cerebellar inclusions positive for two markers of pathological α-synuclein processing. Overall mutant Gba1 expression within Synergy mice does not worsen the behaviour or the histopathological findings associated with overexpression of human α-synuclein in SNCA mice. ...
Parkinsons disease (PD) is a common and incurable neurodegenerative disorder. Loss of midbrain dopaminergic neurons (mDA) of the substantia nigra is the key pathological event in this disorder, but why this cell loss occurs remains a mystery. Much progress has been made by studying genes mutated in inherited forms of PD, thereby identifying cell pathways that might contribute to neuronal death (Hardy, 2010). One such gene is SNCA which encodes α-synuclein. Point mutations and multiplications of SNCA cause familial PD, and variation at this locus is linked with the common sporadic form of the disease. Furthermore, α-synuclein protein is the main component of Lewy bodies: cytoplasmic inclusions seen in mDA neurons that define the disease pathologically. Thus, α-synuclein appears to play a central role in PD pathogenesis. However, studying how it exerts its toxicity has been hampered by the inaccessibility of diseased neurons from patients with the condition, and cell culture systems and ...
In this special issue of Neuropathology and Applied Neurobiology on synucleinopathies, leading investigators provide an overview of this vibrating field. A basic understanding is at hand and it appears increasingly likely that safe and effective mechanism-based therapies for synucleinopathies will be developed. They will probably be aimed at prevention rather than at treating already existing disease. PD stands out among neurodegenerative diseases, in that an effective symptomatic therapy in the form of dopamine replacement already exists. In the first contribution, Roger Barker and Caroline Williams-Gray provide a comprehensive overview of the clinical features of PD and compare them with those of other synucleinopathies (1). In the second article, Nadia Stefanova and Gregor Wenning focus on the rarer, but more aggressive, MSA, which is divided into parkinsonian (MSA-P) and cerebellar (MSA-C) forms, with many cases having features of both (mixed-type MSA) (2). Autonomic dysfunction is a major ...
Parkinsons disease (PK) is a disruption of motor function caused by loss of dopamine neurons. PK can be caused by environmental and genetic factors. One protein known to contribute to PK is the protein α-synuclein found in dopamine neurons. Over expression or mutations in α-synuclein can lead to PK. The soil nematode, Caenorhabditis elegans (C. elegans), has been developed as a model for PK by using a transgenically modified strain, which overexpresses the human α-synuclein protein. In this strain, the dopamine neurons, which have been labeled with a green fluorescent protein, were observed by fluorescent microscopy to degenerate after nine days of development. We have discovered that the transgenic strain expresses a locomotory behavioral defect that is indicative of deficient dopamine signaling at day three of development. When wild-type (normal) nematodes encounter their food, which is a bacterial lawn, they slow their locomotory speed. However, the transgenic strain does not exhibit the
Genomic multiplication from the locus-encoding human -synuclein (-syn), a polypeptide with a propensity toward intracellular misfolding, results in Parkinsons disease (PD). this nematode is only 14C17 days, its been useful in its program to illnesses of maturity especially. In this research we exploited the predictive capacity of the bioinformatic directories to discern hereditary elements and/or pathways that may represent heritable susceptibility elements for Parkinsons disease (PD). PD consists of the progressive lack of dopamine (DA) neurons in the substantia nigra, followed by the deposition of proteins into inclusions termed Lewy systems. Central to the forming of Lewy bodies is normally -synuclein (-syn), a polypeptide using a propensity toward intracellular aggregation. Genomic multiplication from the WT -syn locus leads to PD, indicating that overexpression of the protein alone can result in the condition (7). Maintenance of DA neuron homeostasis continues to be hypothesized to make ...
Microscopy of Lewy bodies in Parkinsons disease (PD) suggests they are not solely filamentous deposits of α-synuclein (αS) but also contain vesicles and other membranous material. We previously reported the existence of native αS tetramers/multimers and described engineered mutations of the αS KTKEGV repeat motifs that abrogate the multimers. The resultant excess monomers accumulate in lipid membrane-rich inclusions associated with neurotoxicity exceeding that of natural familial PD mutants, such as E46K. Here, we use the αS 3K (E35K+E46K+E61K) engineered mutation to probe the mechanisms of reported small-molecule modifiers of αS biochemistry and then identify compounds via a medium-throughput automated screen. αS 3K, which forms round, vesicle-rich inclusions in cultured neurons and causes a PD-like, l-DOPA-responsive motor phenotype in transgenic mice, was fused to YFP, and fluorescent inclusions were quantified. Live-cell microscopy revealed the highly dynamic nature of the αS ...
Alpha synuclein is normally found in neurons, particularly at synapses. When it misfolds, it begins to cause damage. To directly test the gut to brain hypothesis, the researchers injected misfolded alpha synuclein fibrils directly into the muscular wall of the gut in mice, at the point where the stomach empties into the first part of the small intestine, called the duodenum. These fibrils began interacting with the alpha synuclein found in local nerves in the gut, triggering a further misfolding process.. One month later, the researchers found misfolded alpha synuclein in the brain, specifically at the point at which the vagus nerve originates. Within 3 months, misfolded alpha synuclein could be found in other parts of the brain, including the substantia nigra, the main dopamine centre which is involved in movement, and by 7 months, alpha synuclein could clearly be seen in this region.. The team then addressed the effects of cutting the vagus nerve in mice that had been injected with preformed ...
Spark Therapeutics Enters into Definitive Merger Agreement with Roche Spark Therapeutics announced that it has entered into a definitive merger agreement for Roche to fully acquire Spark Therapeutics at a price of $114.50 per share in an all-cash transaction. [Spark Therapeutics, Inc.] Press Release AbbVie and Voyager Therapeutics Announce Collaboration to Develop Vectorized Antibodies to Treat Parkinsons Disease and Other Synucleinopathies AbbVie and Voyager Therapeutics, Inc. announced an exclusive, global strategic collaboration and option agreement to develop and commercialize vectorized antibodies directed at pathological species of alpha-synuclein for the potential treatment of Parkinsons disease and other diseases (synucleinopathies) characterized by the abnormal accumulation of misfolded alpha-synuclein protein. [AbbVie Inc.] Press Release CRISPR Therapeutics and StrideBio Expand Exclusive Development and Option Agreement CRISPR Therapeutics and StrideBio, Inc. announced that a ...
The aggregation of α-synuclein (α-Syn) is a characteristic of Parkinson’s disease (PD). α-Syn oligomerization/aggregation is accelerated by the serine peptidase, prolyl oligopeptidase (POP). Factors that affect POP conformation, including most of its inhibitors and an impairing mutation in its active site, influence the acceleration of α-Syn aggregation resulting from the interaction of these proteins. It is noteworthy, however, that α-Syn is not cleaved by POP. Prolyl endopeptidase-like (PREPL) protein is structurally related to the serine peptidases belonging to the POP family. Based on the α-Syn–POP studies and knowing that PREPL may contribute to the regulation of synaptic vesicle exocytosis, when this protein can encounter α-Syn, we investigated the α-Syn–PREPL interaction. The binding of these two human proteins was observed with an apparent affinity constant of about 5.7 μM and, as in the α-Syn assays with POP, the
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Hi LuSampieri,. It seems like many commonly used immortalized human cells, including HEK293 and HeLa, do express alpha synuclein.. Check out this paper for more details.. Good luck.. ...
Expression of α-Synuclein and clathrin in Z310 cells with or without a-Syn treatment in a typical experiment (n = 5). Z310 cells are immortalized rat choro
Our study recommends the use of low protein binding tubes for quantification in CSF (without additives) of all relevant CSF biomarkers. Pre-analytical factors have less effect on α-synuclein, neurogranin trunc P75, and total tau, as compared to Aβ(1-42). The ratio of Aβ(1-42)/Aβ(1-40), but not Aβ(1- …
Mitochonchrion depicted. The breakdown of dopamine produces many reactive oxygen species: molecules containing oxygen with no free electrons. An excess of reactive oxygen species could halt the mitochondrial respiratory cycle. Because of this, dopaminergic neurons may be more susceptible than other neurons to similar levels of mitochondrial dysfunction, which may explain why PD symptoms first arise in dopaminergic areas of the brain.. Many of the genes involved in familial Parkinsons cases are associated with, or affected by, mitochondrial function. For instance, the amount of alpha-synuclein protein, which aggregates to form Lewy bodies and is mutated many familial cases of PD, increases in response to mitochondrial dysfunction under non-disease conditions. This suggests that sporadic cases of PD arise from failure of mitochondrial function (due to environmental factors) and its resulting downstream effects (e.g. protein aggregates). Rotenone, a pesticide similar in structure to MPTP, inhibits ...
Summary: The authors review the α-synuclein structural, biophysical and biochemical properties that influence relevant mitochondrial physiological processes such as fusion-fission, transport and clearance, and propose that α-synuclein contributes to the mitochondrial defects that are associated with Parkinsons disease. ...
Alpha-synuclein is expressed principally in the central nervous system (brain) but is also expressed in low concentrations in a variety of tissues…
Alpha-synuclein is expressed principally in the central nervous system (brain) but is also expressed in low concentrations in a variety of tissues…
ウサギ・ポリクローナル抗体 ab51104 交差種: Hu 適用: WB,ELISA,IHC-P…Alpha-synuclein抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
... beta-amyloid, and alpha-synuclein". J. Biol. Chem. (39th ed.). 286 (39): 34088-34100. doi:10.1074/jbc.m111.243907. PMC 3190826 ... Prychitko TM, Moore WS (2000). "Comparative evolution of the mitochondrial cytochrome b gene and nuclear beta-fibrinogen intron ... amyloid beta (A4) precursor protein) through reconstituted complex. DUF4602 (PF15375) is generally 120+ amino acids long. There ... The secondary structure of these proteins primarily consist of alpha helices and coils with a small percentage of beta strands ...
However, its protein secondary structure is mostly composed of coiled-coil regions with beta strands and alpha helices found ... and alpha-synuclein". J Biol Chem. 286 (39): 34088-34100. doi:10.1074/jbc.M111.243907. PMC 3190826. PMID 21832049. Huttlin EL, ... 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, ...
... of AD clinical trials of metal chaperones targeting metal-induced aggregation of beta-amyloid in AD and of alpha-synuclein and ... 1987). "The amyloid beta protein gene: cDNA cloning, mRNA distribution, and genetic linkage near the Alzheimer locus". Science ... Tanzi also discovered that beta-amyloid plays a functional role in the brain as an anti-microbial peptide, supporting a role ... Tanzi demonstrated a key role for zinc, copper, and iron in beta-amyloid deposition and Lewy body formation. This finding has ...
... is a synuclein protein found primarily in brain tissue and is seen mainly in presynaptic terminals. Beta- ... 2005). "beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein". J. Biol. Chem. 280 (9): 7562 ... 2006). "Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression". Hum. Mol. Genet ... Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel ...
With his laboratory, he also conducted extensive research on the second pathogenic component, senile plaques of beta-amyloid (A ... Synuclein Mice (with Silke Nuber PhD, Alice Y. Nam BS, Molly M. Rajsombath BS, Haley Cirka Xiaoping Hronowski PhD, Junmin Wang ... Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies (with John B ... Amyloid beta-peptide is produced by cultured cells during normal metabolism: a reprise (2006) The ups and downs of Abeta (2006 ...
Synuclein. *Alpha-synuclein. *Beta-synuclein. *Gamma-synuclein. Other. *Agrin. *Chimerin. *Granin *Chromogranin A ...
PCDHB13‏ (Protocadherin beta 13) هوَ بروتين يُشَفر بواسطة جين PCDHB13 في الإنسان.[1][2] ... PCDHB13, PCDH-BETA13, protocadherin beta 13. معرفات خارجية. الوراثة المندلية البشرية عبر الإنترنت 606339 HomoloGene: 128504 ... Vanhalst K، Kools P، Vanden Eynde E، van Roy F (2001). "The human and murine protocadherin-beta one-exon gene families show ...
Nagase T، Ishikawa K، Kikuno R، وآخرون. (2000). "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.". DNA Res. 6 (5): 337-45. PMID 10574462. doi:10.1093/dnares/6.5.337. الوسيط ...
Fukuda A، Tokonabe S، Hamada M، Matsumoto M، Tsukui T، Nogi Y، Hisatake K (April 2003). "Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH". The Journal of Biological Chemistry. 278 (17): 14827-31. PMID 12590132. doi:10.1074/jbc.M213172200. ...
Ciosk R، Shirayama M، Shevchenko A، Tanaka T، Toth A، Shevchenko A، Nasmyth K (2000). "Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins". Molecular Cell. 5 (2): 243-54. PMID 10882066. doi:10.1016/S1097-2765(00)80420-7. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription ...
"Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments". J. Biol. Chem. ...
Nagase T، Seki N، Ishikawa K، وآخرون. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321-9, 341-54. PMID 9039502. doi:10.1093/dnares/3.5.321. ...
Nagase T، Ishikawa K، Nakajima D، Ohira M، Seki N، Miyajima N، Tanaka A، Kotani H، Nomura N، Ohara O (Apr 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 4 (2): 141-50. PMID 9205841. doi:10.1093/dnares/4.2.141. ...
Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor ... In Alzheimer's disease, these are amyloid-beta and tau. In Parkinson's disease, it is alpha-synuclein. In Huntington's disease ... Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ...
Mutations of synuclein alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Excessive activity of the crinophagy form of autophagy in the insulin-producing beta cells of the pancreas could reduce the ... The Road to Alpha-Synuclein Oligomerization in PD". Parkinson's Disease. 2011: 693761. doi:10.4061/2011/693761. PMC 3026982. ...
The KIAA1211L protein predicted secondary structure is composed of 50% alpha helixes, 8.9% beta sheets, and 17.9% turns. The ... KIAA1211L protein is also predicted to interact with Alpha-synuclein (SNCA), E3 Ubiquitin-Protein Ligase Mdm2 (MDM2), Serine/ ... Glycogen Synthase Kinase 3 Beta (GSK3B) GSK3B is a protein kinase that regulates transcription factors and microtubules. As ... "GSK3B - Glycogen synthase kinase-3 beta - Homo sapiens (Human) - GSK3B gene & protein". www.uniprot.org. Retrieved 2017-04-23. ...
In an alpha-synuclein overexpressing Drosophila model of PD, vorinostat (as well as sodium butyrate) reduced alpha-synuclein- ... and by amyloid-beta senile plaques amyloid-beta senile plaques. Several genetic factors have been identified as contributing to ... Hallmarks include mutations to the alpha-synuclein gene, SNCA, as well as PARK2, PINK1, UCHL1, DJ1, and LRRK2 genes, and ... ncRNA that is encoded antisense from an intron within the beta-amyloid cleaving enzyme gene, BACE1, is involved in AD.[5] This ...
Alzheimer's disease and amyloid-beta PET imaging[edit]. More than 44 million people worldwide have been diagnosed with some ... tau and a-synuclein) has been demonstrated in vitro.[13] Initial single-center studies demonstrated the potential for ... Syed, Y.Y. and E. Deeks, 18F-Florbetaben: A Review in beta-Amyloid PET Imaging in Cognitive Impairment. CNS Drugs, 2015 ... 2015). "Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: Phase 3 study". Alzheimer's & Dementia. 11 ...
... and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions ... 2002). "alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling ... The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse ... 2001). "Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death". Diabetes. 50 (1): 77-82. doi:10.2337/ ...
Elevated levels of beta amyloid, as well as an elevation in the ratio of beta amyloid 42 to the shorter major species of beta ... Suh YH; Checler F (September 2002). "Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and ... An increasing variety of compounds that reduce beta amyloid levels are being identified. Several of these compounds have beta ... Of particular importance is the longer species of beta amyloid known as beta amyloid 42. ...
Syed, Y.Y. and E. Deeks, 18F-Florbetaben: A Review in beta-Amyloid PET Imaging in Cognitive Impairment. CNS Drugs, 2015 Sabri, ... Highly selective binding for β-amyloid over other proteins (e.g., tau and a-synuclein) has been demonstrated in vitro. Initial ... February 2008). "Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism". ... January 2015). "Ethnic comparison of pharmacokinetics of (18)F-florbetaben, a PET tracer for beta-amyloid imaging, in healthy ...
Li W, Lee MK (June 2005). "Antiapoptotic property of human alpha-synuclein in neuronal cell lines is associated with the ... "Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin ...
In these cases, the FD cells express FD-cell markers (e.g. CD21, CD23, CD35, clusterin, podoplanin, gamma-synuclein) and in >90 ... beta-catenin (22.9%), TP53 (22.7%), and ECSIT (19.3%). These genes regulate cell growth and survival. Other genes (e.g. JAK3, ...
Sharma N, Brandis KA, Herrera SK, Johnson BE, Vaidya T, Shrestha R, Debburman SK (2006). "alpha-Synuclein budding yeast model: ... "Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants". The Journal of ... α-synuclein, the major protein component of Lewy bodies, under conditions of low proteasome activity.[97] Impaired proteasomal ...
Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B (1999). "alpha-Synuclein shares physical and ... TGF beta 1.[17]. See also[edit]. *14-3-3 protein. References[edit]. *^ a b c ENSG00000108953 GRCh38: Ensembl release 89: ...
Waking is usually characterized by beta (12-30 Hz) and gamma (25-100 Hz) depending on whether there was a peaceful or stressful ... mainly when they are characterized by abnormal accumulation of alpha-synuclein, such as multiple system atrophy (MSA), ... During sleep, metabolic waste products, such as immunoglobulins, protein fragments or intact proteins like beta-amyloid, may be ... In EEG recordings, REM sleep is characterized by high frequency, low amplitude activity and spontaneous occurrence of beta and ...
Lymphotoxin beta receptor. *MCM2. *Microphthalmia-associated transcription factor. *Muscarinic acetylcholine receptor M2 ...
"Identification of a Wnt/Dvl/beta-Catenin --, Pitx2 pathway mediating cell-type-specific proliferation during development.". ...
"Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction ...
San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein ... "Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinsons disease by ... "A-synuclein is viewed as central to Parkinsons disease pathogenesis. The question has been: could B-synuclein also promote ... San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein ...
... is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly ... Fasudil attenuates aggregation of ?-synuclein in models of Parkinsons disease.. 27098685. 2016. ?-Synuclein Mutation Inhibits ... Abnormal Salivary Total and Oligomeric Alpha-Synuclein in Parkinsons Disease.. 27004367. 2016. Extracellular ?-synuclein--a ... the aggregation of alpha-synuclein results in toxicity because of loss of necessary alpha-synuclein function at the presynaptic ...
... the research activities are concentrated on the role of alpha and beta-synuclein in pathogenesis of PD and AD, to explore new ...
Mouse monoclonal beta Synuclein antibody [6A10]. Validated in WB, IHC and tested in Mouse, Rat, Cow. Immunogen corresponding to ... Lanes 2-7 : Anti-beta Synuclein antibody [6A10] (ab277630) at 1/1000 dilution. Lane 1 : Molecular weight ladder. Lane 2 : rat ... Perfusion-fixed, free floating sections of mouse hippocampus section stained for beta Synuclein using ab277630 (green) at 1/500 ... Synthetic peptide corresponding to Human beta Synuclein aa 113-134 (C terminal) conjugated to keyhole limpet haemocyanin. ...
There are no specific protocols for Recombinant Human beta Synuclein protein (ab48853). Please download our general protocols ...
Invitrogen Anti-Synuclein alpha/beta Recombinant Monoclonal (ST05-21), Catalog # MA5-32176. Tested in Western Blot (WB), ... Protein Aliases: Alpha-synuclein; Beta-synuclein; NACP; non A-beta component of AD amyloid; Non-A beta component of AD amyloid ... Synuclein alpha/beta Recombinant Rabbit Monoclonal Antibody (ST05-21). View all (5) Synuclein alpha/beta antibodies ... Immunocytochemical analysis of Synuclein alpha/beta in SH-SY-5Y cells using a Synuclein alpha/beta Monoclonal antibody (Product ...
alpha-Synuclein protects SH-SY5Y cells from dopamine toxicity.. Colapinto M, Mila S, Giraudo S, Stefanazzi P, Molteni M, ... A broken alpha -helix in folded alpha -Synuclein.. Chandra S, Chen X, Rizo J, Jahn R, Südhof TC. The Journal of biological ... α/β Synuclein - 128 002. Protein involved in Parkinsons and Alzheimers Disease. Polyclonal rabbit antiserum ... Brain alpha-synuclein accumulation in multiple system atrophy, Parkinsons disease and progressive supranuclear palsy: a ...
We discuss the possibility of a pathogenic role for CNTF and a protective role for beta-synuclein in experimental ... Possible implication of ciliary neurotrophic factor (CNTF) and beta-synuclein in the ammonia effect on cultured rat astroglial ... among which the significant increase in beta-synuclein was confirmed by Western blot. DNA microarray data filtration by ... The significant increase in alpha-synuclein mRNA was confirmed by quantitative RT-PCR, but no change was observed in alpha- ...
... beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the ... precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated wit … ... A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in ... More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in ...
... beta (SNCB, beta Synuclein, Phosphoneuroprotein 14, PNP14), item number: S9501-02G.100 from United States Biological at Biomol ... Product information "Anti-Synuclein, beta (SNCB, beta Synuclein, Phosphoneuroprotein 14, PNP14)" Alpha synuclein is an abundant ... Customer review for "Anti-Synuclein, beta (SNCB, beta Synuclein, Phosphoneuroprotein 14, PNP14)" ... A synthetic peptide (IEPLMEPEGSYEDPPQE) of human beta synuclein protein (aa: 108-125) conjugated to diphteria toxid.. ...
... provides in depth analysis on Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or ... Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Pipeline Review, H2 2016, ... Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Products under ... Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Products under ...
beta-Synuclein Recombinant Protein, Novus Biologicals. beta-Synuclein Recombinant Protein, Novus Biologicals. Supplier: Novus ... The Recombinant Human beta-Synuclein Protein from Novus Biologicals is derived from E. coli. The Recombinant Human beta- ...
Effect of naturally occurring α-synuclein-antibodies on toxic α-synuclein-fragments , Synuclein Products ... October 2018 - Frontiers: Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation , Synuclein Products ... We offer a large selection of Beta Amyloids, Taus, Synucleins, Calmodulins, Custom Products and more. ... 6.18.20 - Parkinsons News Today: Changes in Structure of Alpha-synuclein Seen to Make Protein Prone to Clumping , Synucleins ...
Due to the fact that our beta-amyloids are recombinantly produced, there is a batch to batch consistency in the physical and ...
... proteins and antibodies for research on Alzheimers and Parkinsons disease including alpha-synuclein, beta-amyloid, tau, and ... beta-amyloid, leptin, pro-insulin) in E. coli. ... Beta-amyloid peptides. *Proteins (synuclein, tau, tubulin, ...
Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). ... A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. These ... synuclein beta. Enable Javascript to view the expand/collapse boxes.. Printable PDF Open All Close All ... The SNCB gene provides instructions for making a protein called beta-synuclein. The exact function of this protein is unknown, ...
to C-terminal aa 111-131 of human alpha synuclein. Specificity. alpha Synuclein; not beta synuclein ...
Rabbit Polyclonal Anti-alpha-Synuclein Antibody. Validated: WB, ICC/IF, IHC, IHC-Fr, IHC-P. Tested Reactivity: Human, Mouse, ... Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly ... Green: alpha Synuclein protein stained by alpha Synuclein antibody diluted at 1:250. Red: beta Tubulin 3/ ...read more ... FAQs for alpha-Synuclein Antibody (NBP2-15365). (Showing 1 - 1 of 1 FAQs).. * Im looking for an alpha-Synuclein antibody with ...
2004) Double-knockout mice for alpha- and beta-synucleins: Effect on synaptic functions. Proc Natl Acad Sci USA 101:14966-14971 ... Generation of Synuclein Null Mice.. αβγ-Synuclein triple KO mice lack all murine synucleins and allow us to examine loss-of- ... αβγ-Synuclein triple KOs were crossed to human or mouse wild-type α-synuclein-expressing transgenics (27) to generate synuclein ... Wild-type αβγ-Syn+/+, blue triangle; synuclein null αβγ-Syn−/−, green square; synuclein null rescued by mouse α-synuclein ...
alpha isoform (18 kDa) of synuclein; the antibody may cross-react with beta-synuclein ... Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med ...
The SNCB gene provides instructions for making a protein called beta-synuclein. Learn about this gene and related health ... Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). ... A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. These ... Beta-synuclein gene alterations in dementia with Lewy bodies. Neurology. 2004 Sep 14;63(5):805-11. Citation on PubMed or Free ...
SNCA: synuclein alpha. *SNCB: synuclein beta. *SOD1: superoxide dismutase 1. *SOS1: SOS Ras/Rac guanine nucleotide exchange ...
... alpha-synuclein; amyloid beta precursor protein; amyloid-beta; amyotrophic lateral sclerosis; apolipo-protein E; apoptosis- ...
Furthermore to amyloid beta (A) and tau, -synuclein, most widely known. Furthermore to amyloid beta (A) and tau, -synuclein, ... However, there is a significant relationship between -synuclein and cognition (P = 0.001), with an increase of -synuclein ... synuclein in AD has been further developed by evidence suggesting -synuclein might interact with A and tau, a prodromal stage ... alpha-synuclein, light cognitive impairment (MCI), limited variety of sufferers, lower or more CSF -synuclein in Advertisement ...
Alpha-, Beta- and Gamma-Synucleis. *Mouse Gamma-Synuclein also available. *For research use only ... Recombinant Synuclein proteins are offered for use in research e.g. aggregation experiments or analysis of Lewy body disease ...
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection. ... Synucleins 6. beta-Synuclein 7. Molecular Chaperones (Chaperone, Molecular) 8. Heparin (Liquaemin) ... alpha-Synuclein. Subscribe to New Research on alpha-Synuclein A synuclein that is a major component of LEWY BODIES that plays a ... 07/19/2002 - "This cell system of oligodendroglial alpha-synuclein expression is a useful system to study alpha-synuclein ...
2010) EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc Natl Acad Sci USA 107: ... able to inhibit α-synuclein aggregation. SynuClean-D significantly reduces the in vitro aggregation of wild-type α-synuclein ... mainly composed of the protein α-synuclein. The disordered nature of α-synuclein and its complex aggregation reaction ... significantly reduces the toxicity exerted by α-synuclein. SynuClean-D-treated worms show decreased α-synuclein aggregation in ...
Hypokinesia and reduced dopamine levels in zebrafish lacking beta- and gamma1-synucleins. J Biol Chem. 2012;287(5):2971-2983. ... encoding α-synuclein, modulate both PD risk (5-7) and α-synuclein expression levels (8), suggesting that α-synuclein may be ... Loss of α-synuclein prevents progressive motor deficits in the rotenone model of PD. We next evaluated the role of α-synuclein ... This suggests that α-synuclein may be dispensable, possibly due to compensatory functions of β- and γ-synucleins (62). However ...
... alpha-synuclein (α-syn), and beta 2 microglobulin (β2m), was attempted over the surface of nano-gold colloidal particles, ... The adsorption of amyloidogenic peptides, amyloid beta 1-40 (Aβ1-40), alpha-synuclein (α-syn), and beta 2 microglobulin (β2m), ... Keywords: amyloidogenic peptides; amyloid beta; alpha synuclein; beta 2 microglobulin; nano-gold colloids; peptide coverage; ... alpha synuclein; beta 2 microglobulin; nano-gold colloids; peptide coverage; aggregation; adsorption orientation; spiking-out ...
We refer to the 140 and 134 amino acid proteins as alpha-synuclein and beta-synuclein, respectively. Both synucleins are ... with the precursor of the non-A beta component of Alzheimers disease amyloid which in turn is highly homologous to synuclein ... Identification of two distinct synucleins from human brain.. Jakes R1, Spillantini MG, Goedert M. ... The previously unrecognised homology between these two proteins defines a family of human brain synucleins. ...
The protein alpha-synuclein is implicated in the etiology of both sporadic and hereditary Parkinsons disease. Structural ... 2000) Parkinsons disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed ... inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J Biol Chem 277:11970-11978PubMedGoogle Scholar ... Comparative structural studies of the other human synuclein family members, β-synuclein and γ-synuclein have also been ...
Alpha, Beta - Synuclein antibody [3B6] Mouse Monoclonal Hu, Ms, Rat ELISA, WB, WB-Ag ... alpha Synuclein antibody [4D6] Mouse Monoclonal Hu, Ms, Rat ELISA, IHC, IHC-Fr, IHC-P, WB ... alpha Synuclein antibody [4B12] Mouse Monoclonal Hu Dot, ELISA, IHC, IHC-Fr, IHC-P, WB ... alpha Synuclein antibody Rabbit Polyclonal Hu, Ms, Rat ICC/IF, IHC-Fr, IHC-P, WB ...
Selective binding to alpha-synuclein-rich brain tissue (versus amyloid-beta or tau-rich tissue) ... MJFF launched the Ken Griffin Alpha-Synuclein Image Competition to spur a scientific race in pursuit of an alpha-synuclein ... The Michael J. Fox Foundation has long supported the pursuit of an alpha-synuclein PET tracer - in addition to funding alpha- ... In vivo imaging of alpha-synuclein pathology could be useful as a biomarker for the presence of disease and disease progression ...
  • Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinson's disease by being mutated or over-expressed," said La Spada. (ucsd.edu)
  • Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. (nih.gov)
  • Alleles 'G' of rs356165 and rs356219 were associated with increased levels of SNCA expression and high alpha-synuclein levels rs356165 and rs356219 variants might influence on Parkinson's disease development by upregulating SNCA expression. (nih.gov)
  • An alpha-synuclein mutant inhibited two forms of endocytosis, slow and rapid, in central nerve terminals. (nih.gov)
  • A-synuclein is viewed as central to Parkinson's disease pathogenesis. (ucsd.edu)
  • When he founded his first CRO, JSW-Lifesciences 1999, the research activities are concentrated on the role of alpha and beta-synuclein in pathogenesis of PD and AD, to explore new therapeutic possibilities. (neuroscios.com)
  • A team of scientists from Japan and the University of California, San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein promote neurodegeneration. (ucsd.edu)
  • In the 2004 study, La Spada and colleagues found that mutations of the naturally occurring B-synuclein protein in DLB patients "were strong strongly suggestive of being pathogenic. (ucsd.edu)
  • The question has been: could B-synuclein also promote neurodegeneration because it's similar in its sequence and expression pattern to A-synuclein? (ucsd.edu)
  • In AD, a peptide derived from alpha synuclein forms an intrinsic component of plaque amyloid. (thermofisher.com)
  • Global Markets Directs, Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Pipeline Review, H2 2016, provides in depth analysis on Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) targeted pipeline therapeutics. (researchmoz.us)
  • The report provides comprehensive information on the Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) , targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchmoz.us)
  • Additionally, the report provides an overview of key players involved in Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) targeted therapeutics development and features dormant and discontinued projects. (researchmoz.us)
  • Due to the fact that our beta-amyloids are recombinantly produced, there is a batch to batch consistency in the physical and chemical properties of all our recombinant beta-amyloid peptides. (rpeptide.com)
  • rPeptide has a proprietary platform vector technology that enables the expression of historically difficult peptides/proteins as soluble peptides/proteins (e.g. beta-amyloid, leptin, pro-insulin) in E. coli . (lubio.ch)
  • C1orf131 has been shown to interact with ubiquitin through affinity capture followed by mass spectrometry and APP (amyloid beta (A4) precursor protein) through reconstituted complex. (wikipedia.org)
  • The 140 amino acid protein is identical with the precursor of the non-A beta component of Alzheimer's disease amyloid which in turn is highly homologous to synuclein from Torpedo electroplaques and rat brain. (nih.gov)
  • Structure within the amyloid fibril form of alpha-synuclein can also provide clues regarding the assembly pathways of the protein. (springer.com)
  • Furthermore to amyloid beta (A) and tau, -synuclein, most widely known for its function in Parkinsons disease (PD), continues to be suggested to be engaged in cognition and pathogenesis of Alzheimers disease (AD). (biodiversityhotspot.org)
  • Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. (frontiersin.org)
  • The implication of alpha synuclein in neurodegenerative diseases started after the identification of non A beta component of amyloid (NAC peptide) in Alzheimeris disease (AD) brains. (genetex.com)
  • Structural features of alpha-synuclein amyloid fibrils revealed by Raman spectroscopy. (amedeo.com)
  • With that kinetic model we have analyzed 41 representative protein aggregation data sets in two recent publications, including amyloid beta, alpha-synuclein, polyglutamine, and prion proteins (Morris, A. M., et al. (ebi.ac.uk)
  • The most common altered proteins associated with neurodegeneration are Hyperphosphorylated tau (HPt), beta amyloid (Aβ), alpha-synclein (αS) and transactive response DNA binding protein 43 (TDP43). (diva-portal.org)
  • One example in Alzheimer's disease is tau protein, an often overshadowed counterpart to the more heavily studied amyloid beta protein. (pbs.org)
  • In Alzheimer's disease, nerve cells lose their connectivity with each other due to the buildup of amyloid plagues made of cleaved amyloid beta protein and neurofibrillary tangles made of tau protein. (pbs.org)
  • Going further, the scientists repeated this experiment, but replaced tau with one of two other proteins that tangle in neurodegenerative disease: alpha-synuclein in Parkinson's disease and amyloid beta in Alzheimer's disease. (pbs.org)
  • They found Cyp40 could break down clumps of alpha-synuclein, but not amyloid beta ones. (pbs.org)
  • Based on their results, the team thinks that CyP40 untangles tau and alpha synuclein proteins by attaching to their hairpin turns, which amyloid beta lacks, and unbends them. (pbs.org)
  • A. " Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid {alpha}-synuclein fibrils ," by Francesco Simone Ruggeri, Fabrizio Benedetti, Tuomas P. J. Knowles, Hilal A. Lashuel, Sergey Sekatskii, and Giovanni Dietler (Vol. 115 No. 28, July 10, 2018, p. 7230-7235). (wisc.edu)
  • Long-range distances in amyloid fibrils of α-synuclein from PELDOR spectroscopy. (mpg.de)
  • The study analyzed the following proteins: beta-amyloid, tau (P-tau), alpha-synuclein and neurofilaments. (innovations-report.com)
  • Amyloid plaques consisting of insoluble agglomerates of beta-amyloid peptide are one of the most obvious features of the disease. (brainblogger.com)
  • Recent research findings demonstrate that the seeds of incorrectly folded beta-amyloid peptides can be transferred from one neuron to another, thus causing progression of the disease. (brainblogger.com)
  • Again, like in the case of beta-amyloid, the seeds of misfolded tau proteins can be transferred between neurons. (brainblogger.com)
  • It seems that acquiring the wrong form of beta-amyloid peptide or tau protein by the cell through one or another mechanism initiates the process of conversion of soluble proteins into insoluble aggregates, leading to damage to the brain functions in general. (brainblogger.com)
  • Biology of tau, synucleins, TDP-43 and amyloid beta precursor proteins (APPs) in health and disease. (upenn.edu)
  • This FOA invites applications that will systematically and comprehensively characterize alpha-synuclein and amyloid-beta subspecies present in human Lewy Body Dementia (LBD) post-mortem brain tissue, identify toxic subspecies and potential mechanisms of toxicity, and characterize any interactions between the proteins that may contribute to increased toxicity and/or explain selective vulnerabilities of cells/circuits. (nih.gov)
  • All applications will be expected to include plans for developing a publicly-available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD. (nih.gov)
  • The purpose of the Lewy Body Dementia Center Without Walls (CWOW) program is ultimately to understand how toxic species of alpha-synuclein and amyloid-beta produce the clinical pathology characteristic of Lewy Body Dementia. (nih.gov)
  • Erica Melief, PhD Dopaminergic influence on amyloid beta. (washington.edu)
  • α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP. (bath.ac.uk)
  • Marta's research is exploring the relationship between amyloid-beta (Aβ) and alpha synuclein (α-synuclein) in Parkinson's disease (PD), DLB and PDD. (bristol.ac.uk)
  • MBS923972 is a ready-to-use microwell, strip plate Sandwich ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the synuclein, alpha (non A4 component of amyloid precursor) (SNCA) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • Determine if nasal swabs can provide an adequate sample for evaluation using cytology and immunohistochemistry for alpha-synuclein, Amyloid-beta (A-beta) and Phospho-tau (p-tau) staining. (clinicaltrials.gov)
  • The limbic and neocortical contribution of alpha-synuclein, tau, and amyloid beta to disease duration in dementia with Lewy bodies. (mayo.edu)
  • Synuclein family of proteins is abundantly expressed in neuronal cytosol and presynaptic terminals. (thermofisher.com)
  • After protein microarray data filtration by signal intensity, x-fold change and z-score, 11 proteins were selected, among which the significant increase in beta-synuclein was confirmed by Western blot. (nih.gov)
  • A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. (nih.gov)
  • Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). (nih.gov)
  • Synucleins are a vertebrate-specific family of abundant neuronal proteins. (pnas.org)
  • Synucleins are a family of vertebrate-specific proteins with three closely related members, α-, β-, and γ-synuclein ( 1 , 2 ). (pnas.org)
  • The secondary structure of these proteins primarily consist of alpha helices and coils with a small percentage of beta strands. (wikipedia.org)
  • The previously unrecognised homology between these two proteins defines a family of human brain synucleins. (nih.gov)
  • We refer to the 140 and 134 amino acid proteins as alpha-synuclein and beta-synuclein, respectively. (nih.gov)
  • The interest on -synuclein in AD has been further developed by evidence suggesting -synuclein might interact with A and tau, two crucial proteins in AD pathogenesis, promoting their mutual aggregation [7C10] amplifying neuronal damage and accelerating cognitive decline [11, 12]. (biodiversityhotspot.org)
  • Collectively the data suggest a previously unknown cascade of events where pathologic α-synuclein leads to a loss of a number of critical presynaptic proteins, thereby inducing functional synaptic deficits. (pubmedcentralcanada.ca)
  • The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. (frontiersin.org)
  • Lewy bodies are composed of truncated and phosphorylated intermediate neurofilament proteins, alpha synuclein, ubiquitin and associated enzymes. (genetex.com)
  • The synuclein phosphoproteins (15-20 kD) are small highly conserved proteins in vertebrates. (genetex.com)
  • The research team is investigating whether and how interaction between the two proteins plays a role in preventing or slowing the build-up of alpha-synuclein. (plymouth.ac.uk)
  • Her work demonstrated that tau, alpha-synuclein and TDP-43 proteins form unique brain aggregates in neurodegenerative diseases and provided critical evidence that aggregation of brain proteins is a common mechanistic theme in diverse neurodegenerative diseases including AD, PD, FTLD, ALS and related disorders. (upenn.edu)
  • The hallmark of DLB is the presence of Lewy bodies , which are intracytoplasmic inclusion bodies that contain synuclein proteins located in the cortical and subcortical neurons. (wikidoc.org)
  • [6] [7] Synuclein proteins are members of a pre-synpatic protein family located in the central and peripheral nervous systems. (wikidoc.org)
  • The recombinant human synuclein family (α-, β-and γ-) and α-synuclein domains (1-60, 1-95, 61-140 and 96-140) proteins were resolved by SDS-PAGE, transferred to PVDF membrane and probed with anti-α-Synuclein (61-95 aa) antibody Cat. (acris-antibodies.com)
  • The following antibody was used in this experiment: Synuclein alpha/beta Recombinant Rabbit Monoclonal Antibody (ST05-21) from Thermo Fisher Scientific, catalog # MA5-32176, RRID AB_2809464. (thermofisher.com)
  • Immunocytochemistry/ Immunofluorescence: alpha-Synuclein Antibody [NBP2-15365] - DIV14 rat E18 primary cortical neurons were fixed in 4% paraformaldehyde at RT for 15 min. (novusbio.com)
  • Immunohistochemistry-Frozen: alpha-Synuclein Antibody [NBP2-15365] - Frozen-sectioned adult mouse hippocampus. (novusbio.com)
  • Green: alpha Synuclein protein stained by alpha Synuclein antibody diluted at 1:250. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded Colon ca, using antibody at 1:250 dilution. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded Rat brain diluted at 1:500. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded rat brain. (novusbio.com)
  • Green: alpha Synuclein antibody diluted at 1:200. (novusbio.com)
  • Immunohistochemistry-Frozen: alpha-Synuclein Antibody [NBP2-15365] - Frozen sectioned E13.5 Rat brain. (novusbio.com)
  • Anti-human alpha-synuclein antibody (Cat. (clontech.com)
  • 18671A, B) is an affinity-purified IgG antibody that recognizes human alpha-synuclein protein. (clontech.com)
  • The antibody was raised in rabbit using a synthetic peptide, and can be used for Western blot (WB) detection or immunohistochemical (IHC) detection of human alpha-synuclein protein. (clontech.com)
  • 9. The method of claim 8 wherein the one or more agents are an antibody that specifically and independently detects and binds with one of neurensin (p24), UCH-L1 or synuclein. (google.ca)
  • The following antibody was used in this experiment: alpha Synuclein Recombinant Polyclonal Antibody (14HCLC) from Thermo Fisher Scientific, catalog # 710110, RRID AB_2532568. (thermofisher.com)
  • The antibody specific for alpha-synuclein does not cross react with beta-synuclein and will be useful for the confirmation of Parkinson's disease and Lewy body dementia and other studies for the localization and detection of alpha-synuclein. (thermofisher.com)
  • Synuclein-alpha (Phospho-Tyr136) Antibody detects endogenous levels of Synuclein-alpha only when phosphorylated at Tyr136. (avivasysbio.com)
  • IHC staining of purified anti-α-Synuclein, 80-96 antibody (clone A15115A) on formalin-fixed paraffin-embedded Parkinson's disease human brain tissue. (biolegend.com)
  • Western blot of purified anti-α-Synuclein, 80-96 antibody (clone A15115A), and isotype-matched IgG1 control, demonstrating the binding specificity of clone A15115A to endogenous and recombinant human α-synuclein. (biolegend.com)
  • IHC staining of α-Synuclein deposits with anti-α-Synuclein, aggregated antibody (clone Syn-O4) on formalin-fixed paraffin-embedded Parkinson's disease brain tissue. (biolegend.com)
  • A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection. (curehunter.com)
  • The accumulation of aggregated alpha-synuclein is a pathological hallmark of Parkinson's and a priority target for drug development given its hypothesized contribution to neurodegeneration. (michaeljfox.org)
  • Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. (lsbio.com)
  • Beta-synuclein aggregates and induces neurodegeneration in dopaminergic neurons. (mpg.de)
  • α-Synuclein immunotherapy blocks uptake and templated propagation of misfolded α-Synuclein and neurodegeneration. (upenn.edu)
  • In PD, an alpha synuclein accumulates in Lewy bodies. (thermofisher.com)
  • The aggregated proteinaceous inclusions called Lewy bodies found in PD and cortical Lewy body dementia (LBD) were discovered to be predominantly alpha-synuclein. (biomol.com)
  • Additionally, α-synuclein is the major component of Lewy bodies, the pathological hallmark of PD ( 10 ). (pnas.org)
  • A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. (nih.gov)
  • Beyer K, Domingo-Sàbat M, Santos C, Tolosa E, Ferrer I, Ariza A. The decrease of β-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies. (nih.gov)
  • Beta-synuclein gene alterations in dementia with Lewy bodies. (nih.gov)
  • Indeed, it was found subsequently that 40C50% of AD patients also present with -synuclein positive Lewy body [2C4] and these patients demonstrate an accelerated cognitive decline [5, 6]. (biodiversityhotspot.org)
  • Several groups have attempted to investigate -synuclein levels in the brain and cerebrospinal fluid (CSF) of sufferers with Advertisement, PD, and dementia with Lewy systems (DLB). (biodiversityhotspot.org)
  • Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by accumulation of α-synuclein (αS) in cytoplasmic inclusions termed Lewy bodies (LB) and neurites, progressive neuron loss, and motor deficits ( Goedert, 2001 ). (jneurosci.org)
  • Pathologic intra-neuronal deposits of α-synuclein are seen in diverse neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and a subset of Alzheimer's disease (AD), and are often accompanied with dementia ( Mukaetova-Ladinska and McKeith, 2006 ). (pubmedcentralcanada.ca)
  • The abnormal aggregation of α-synuclein (α-syn) in the central nervous system defines neurodegenerative diseases such as Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA) ( Spillantini and Goedert, 2000 ). (frontiersin.org)
  • Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. (mdpi.com)
  • Lewy body diseases (LBD) share alpha-synuclein (AS) aggregation and Lewy body (LB) formation as their key pathogenic events. (mdpi.com)
  • There is now a general group of synucleinopathies which implicates alpha synuclein in Lewy body syndromes, Parkinsonis disease, and Alzheimeris disease. (genetex.com)
  • Alpha Synuclein is the major component of Lewy bodies and Lewy neuritis in sporadic PD, dementia with Lewy Bodies and Lewy Body variant of AD. (genetex.com)
  • Antibodies to alpha synuclein provide a specific method to detect Lewy bodies and associated pathological mechanism of PD and AD. (genetex.com)
  • Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinson's disease, Lewy body dementia (associated with both Alzheimer's and Parkinson's disease), and multiple system atrophy. (clontech.com)
  • a-Synuclein is also the main component of pathogenic Lewy bodies and Lewy neurites. (biomol.com)
  • Alpha-Synuclein is involved in the formation of SNARE complexes, and most significantly, aggregated alpha-synuclein is one of the major components found in the Lewy bodies that occur in Parkinson's disease (PD) and other neurodegenerative disorders. (thermofisher.com)
  • In addition, alpha-synuclein protein is the main component of Lewy bodies, the pathological signature for PD. (yale.edu)
  • Alpha-synuclein fibrils are major substituent of the intracellular Lewy bodies seen in Parkinson rsquo;s disease. (acris-antibodies.com)
  • α-synuclein fibrils are a major component of the intracellular Lewy bodies that are associated with Parkinson's disease, Lewy body dementia, and multiple system atrophy. (biolegend.com)
  • α-synuclein is present in all nerve cells but becomes abnormally aggregated and forms Lewy bodies in PD, PDD and DLB. (bristol.ac.uk)
  • Miners, J, Renfrew, R, Swirski, M & Love, S, 2014, Accumulation of α-synuclein in dementia with Lewy bodies is associated with decline in the α-synuclein-degrading enzymes kallikrein-6 and calpain-1 . (bristol.ac.uk)
  • Beta-synuclein regulates Akt activity in neuronal cells. (wikipedia.org)
  • Alpha synuclein is an abundant 140 amino acid neuronal protein, expressed primarily at. (biomol.com)
  • Deletion of synucleins causes alterations in synaptic structure and transmission, age-dependent neuronal dysfunction, as well as diminished survival. (pnas.org)
  • Using these mice, we show that synuclein deficiency leads to altered synapse structure and physiology, age-dependent neuronal dysfunction, and impaired survival. (pnas.org)
  • Several neurodegenerative diseases are typified by intra-neuronal α-synuclein deposits, synaptic dysfunction and dementia. (pubmedcentralcanada.ca)
  • Under physiologic conditions α-synuclein localizes to presynapses, and in pathologic states α-synuclein accumulations are seen in cell bodies, neuronal processes as well as synapses ( Roy, 2009 ). (pubmedcentralcanada.ca)
  • The alpha and beta synucleins are found primarily in brain tissue where they are seen mainly in neuronal cytosol and presynaptic terminals. (thermofisher.com)
  • a-Synuclein (amino acids 1-140), an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded with an extended structure primarily composed of random coils. (prospecbio.com)
  • a-synuclein has been suggested to be implicated in the pathogenesis of Parkinson's disease and related neurodegenerative disorders, and more recently, to be an important regulatory component of vesicular transport in neuronal cells. (prospecbio.com)
  • Pathophysiological consequences of neuronal alpha-Synuclein overexpression: Impacts on ion homeostasis, stress signaling, mitochondrial integrity, and electrical activity. (mpg.de)
  • Significantly, Dr. Lee's studies implicated the abnormal aggregation of tau, alpha-synuclein and TDP-43 in mechanisms that compromise neuronal viability. (upenn.edu)
  • Neuronal α-synuclein is concentrated in presynaptic nerve terminals, interacts with plasma membrane phospholipids, and is also present in nuclei and mitochondria. (biolegend.com)
  • Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term. (upenn.edu)
  • Alpha-synuclein is encoded by the SNCA gene in humans and is mainly expressed in the cerebral neocortex, hippocampus, nigra, thalamus, and metencephalon, with the majority of the protein localizing to the presynaptic terminal and nucleus of neuron cells. (clontech.com)
  • Mutations of α-synuclein ( SNCA ) gene have been classically associated with Parkinson's disease with dementia (PDD), but triplication defects and mutations of the E46K and A53T loci within the SNCA gene have been described in patients with DLB. (wikidoc.org)
  • The human alpha-synuclein protein is made of 140 amino acids, encoded by the SNCA gene. (acris-antibodies.com)
  • Structural studies of both the intrinsically disordered free state of the protein and of more ordered states, adopted when alpha-synuclein self assembles into fibrils or binds to lipid membranes or detergent micelles, have begun to provide insights into factors that likely influence both the pathological aggregation of the protein and its normal functions. (springer.com)
  • Importantly, the accumulation of -synuclein alone has also been shown to significantly disrupt cognition in mice [12, 13], as well as be associated with cognitive impairment or dementia in synucleinopathies [14, 15]. (biodiversityhotspot.org)
  • Though it is evident that excessive α-synuclein has an overall deleterious role in human disease, the precise cascade of early pathologic events resulting from elevations of h-α-syn, and culminating in eventual synaptic dysfunction and dementia are unclear ( Cookson and van der Brug, 2008 ). (pubmedcentralcanada.ca)
  • Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. (nih.gov)
  • Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. (nih.gov)
  • Dot Blots of anti-α synuclein antibodies (clone Syn-O4 and 4B12/synuclein), demonstrating their binding to α-synuclein conformers (monomeric and fibrillar). (biolegend.com)
  • In vivo imaging of alpha-synuclein pathology could be useful as a biomarker for the presence of disease and disease progression and as a pharmacodynamic tool for drug development. (michaeljfox.org)
  • In vivo binding patterns consistent with the expected distribution of alpha-synuclein pathology per population (e.g. (michaeljfox.org)
  • Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease. (yale.edu)
  • This is one of the first studies to use supercomputers to model how alpha-synuclein complexes damage the cells, and how that could be blocked," said Eliezer Masliah, professor of neurosciences and pathology at UC San Diego. (innovations-report.com)
  • Beta-synuclein is a protein that in humans is encoded by the SNCB gene. (wikipedia.org)
  • The SNCB gene provides instructions for making a protein called beta-synuclein. (nih.gov)
  • The Recombinant Human beta-Synuclein Protein from Novus Biologicals is derived from E. coli. (vwr.com)
  • The Recombinant Human beta-Synuclein Protein has been validated for the following applications: SDS-Page. (vwr.com)
  • Recombinant human alpha synuclein, produced in E.coli. (genetex.com)
  • The Recombinant Human a-Synuclein is purified by proprietary chromatographic techniques. (prospecbio.com)
  • The protein encoded by this gene is highly homologous to alpha-synuclein. (wikipedia.org)
  • A point mutation in the gene coding for the alpha-synuclein protein was the first discovery linking this protein to a rare familial form of Parkinson's disease (PD). (biomol.com)
  • Subsequently, other mutations in the alpha-synuclein gene have been identified in familial PD. (biomol.com)
  • α-Synuclein has been the focus of intense attention since the identification of dominant mutations and gene multiplications that link it to familial Parkinson's disease (PD) ( 7 ). (pnas.org)
  • Recently, strong ties between the α-synuclein gene and sporadic PD have emerged in genomewide association studies, making α-synuclein the most broadly relevant PD gene ( 8 , 9 ). (pnas.org)
  • 1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. (springer.com)
  • Certain missense mutations in the alpha synuclein gene (A53T, A30P) have been linked to the familial Parkinsonis disease (PD). (genetex.com)
  • Mutations of the a-synuclein gene have been linked to Parkinson disease. (biomol.com)
  • Mutation of the alpha-synuclein gene is associated with familial forms of PD. (thermofisher.com)
  • The first PD gene to be identified was the alpha-synuclein gene. (yale.edu)
  • Three point mutations and gene multiplications link alpha-synuclein to familial PD. (yale.edu)
  • Predisposition to DLB may be caused by autosomal dominant genetic mutations of the Synuclein gene family. (wikidoc.org)
  • Abnormal processing of alpha-synuclein is predicted to lead to pathological changes in its binding properties and function (1). (biomol.com)
  • Alpha-Synuclein is a small, presynaptic protein that is the major nonamyloid component of the pathological inclusions characteristic of a wide range of neurodegenerative disorders, collectively known as synucleinopathies. (thermofisher.com)
  • The late onset phenotypes in synuclein null mice were not due to a loss of synapses or neurons but rather reflect specific changes in synaptic protein composition and axonal structure. (pnas.org)
  • Together, the high sequence homology, structural conservation, and overlapping expression pattern of synucleins strongly suggest redundant synaptic functions. (pnas.org)
  • Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. (semanticscholar.org)
  • Alpha-Synuclein belongs to the Synuclein family, which includes beta and gamma Synuclein, and is predominantly expressed in neurons, and concentrated at synaptic terminals. (thermofisher.com)
  • Synucleins may be involved in the regulation of dopamine release and transport and the modulation of synaptic vesicle function. (thermofisher.com)
  • Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). (nih.gov)
  • Towards this, we developed a quantitative model-system to evaluate evolving α-synuclein-induced pathologic events with high spatial and temporal resolution, using cultured neurons from brains of transgenic mice over-expressing fluorescent-human-α-synuclein. (pubmedcentralcanada.ca)
  • Beta-synuclein is suggested to be an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases such as Parkinson's disease. (wikipedia.org)
  • Brain alpha-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation. (sysy.com)
  • α-Synuclein has been the focus of intense attention since mutations in it were identified as a cause for familial Parkinson's disease. (pnas.org)
  • Our results demonstrate that synucleins contribute importantly to the long-term operation of the nervous system and that alterations in their physiological function could contribute to the development of Parkinson's disease. (pnas.org)
  • The protein alpha-synuclein is implicated in the etiology of both sporadic and hereditary Parkinson's disease. (springer.com)
  • The ability to image alpha-synuclein deposition in the brain would be a game-changing achievement for the Parkinson's disease field. (michaeljfox.org)
  • The aggregation of α-synuclein (α-syn) is inseparably connected to Parkinson's disease (PD). (frontiersin.org)
  • Parkinson's disease and multiple system atrophy have distinct alpha-synuclein seed characteristics. (amedeo.com)
  • A-Synuclein A53T Human Recombinant which is a Parkinson's disease-related point mutant, produced in E.Coli is a single, non-glycosylated polypeptide chain of 140 amino acids having a molecular mass of 14.4kDa (molecular size on SDS-PAGE will appear higher). (prospecbio.com)
  • The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease. (mpg.de)
  • We believe that these ring- or pore-like structures might be deleterious to the cells, and we have a unique opportunity to better understand how alpha-synuclein is involved in the pathogenesis of Parkinson's disease, and how to reverse this process. (innovations-report.com)
  • Comparative structural studies of the other human synuclein family members, β-synuclein and γ-synuclein have also been performed to clarify features that differentiate them from alpha-synuclein in both pathological and functional contexts. (springer.com)
  • As the impact of this pathological spreading mechanism is currently debated, we aimed to investigate the transfer and subcellular location of alpha-synuclein species in a novel 3D co-culture human cell model based on highly differentiated SH-SY5Y cells. (diva-portal.org)
  • The physiological function of alpha-synuclein appears to require its translocation between these subcellular compartments and interconversion between the 2 conformations. (biomol.com)
  • The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. (clontech.com)
  • Over-expression of alpha-synuclein in the nervous system enhances axonal degeneration after peripheral nerve lesion in a transgenic mouse strain. (sysy.com)
  • An allele of alpha synuclein has been linked to many familial cases of PD. (thermofisher.com)
  • The presynaptic localization and function of synucleins may also have a bearing on PD, as synapses are lost early in disease progression ( 11 ). (pnas.org)
  • Determining nuclear localization of alpha-synuclein in mouse brains. (lsbio.com)
  • The research is titled "Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species. (digitaljournal.com)
  • The oxidative stress-related reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown to promote formation of alpha-synuclein oligomers in vitro. (diva-portal.org)
  • Both circular dichroism (CD) and Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy showed that the formation of HNE- and ONE-induced oligomers coincided with a spectral change from random coil to beta-sheet. (diva-portal.org)
  • However, ONE-induced alpha-synuclein oligomers exhibited a slightly higher degree of beta-sheet. (diva-portal.org)
  • These neurodegenerative multisystem disorders have widespread occurrence of α-synuclein containing deposits in the central, peripheral, and autonomic systems. (pathologyoutlines.com)
  • We provide the average nucleation (k(1)) and growth (k(2)) rate constants and correlations with variable temperature or varying pH for the protein alpha-synuclein. (ebi.ac.uk)
  • The Michael J. Fox Foundation is sponsoring a $2 million prize to the first team that develops a viable selective alpha-synuclein PET tracer and agrees to make that tracer available broadly. (michaeljfox.org)
  • Size exclusion chromatography showed that after 1 h of incubation, HNE induced the formation of an oligomeric alpha-synuclein peak with a molecular weight of about similar to 2000 kDa, which coincided with a decreasing similar to 50 kDa monomeric peak. (diva-portal.org)
  • Seeking a mechanism for the toxicity of oligomeric alpha-synuclein. (bath.ac.uk)
  • Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals. (nih.gov)
  • Synucleins have overlapping expression patterns and are enriched in presynaptic termini ( 5 , 6 ). (pnas.org)
  • Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. (springer.com)
  • Despite their disease relevance, the normal physiological function of synucleins has remained elusive. (pnas.org)
  • Autophagy is involved in the intracellular degradation of aggregation-prone α-synuclein ( 6 ) and huntingtin ( 7 , 8 ). (pubmedcentralcanada.ca)
  • Moreover, recent studies have shown that a-synuclein has chaperone activity and that this activity is lost upon removing its C-terminal acidic tail (amino acids 96-140). (prospecbio.com)
  • a-Synuclein Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain of 140 amino acids having a molecular mass of 14.4kDa (Real molecular weight on SDS-PAGE will be shift up). (prospecbio.com)
  • KLH-Conjugated synthetic peptide that included amino acid residues 80-96 of human α-synuclein. (biolegend.com)
  • More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. (nih.gov)
  • Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. (nih.gov)
  • Synthetic peptide corresponding to Human beta Synuclein aa 113-134 (C terminal) conjugated to keyhole limpet haemocyanin. (abcam.com)
  • Perfusion-fixed, free floating sections of mouse hippocampus section stained for beta Synuclein using ab277630 (green) at 1/500 dilution, and counterstained with rabbit pAb to C-terminal peptide of rat NF-L (red) at 1/5000 dilution in immunohistochemical analysis. (abcam.com)
  • A synthetic peptide (IEPLMEPEGSYEDPPQE) of human beta synuclein protein (aa: 108-125) conjugated to diphteria toxid. (biomol.com)
  • The antiserum was produced against synthesized peptide derived from human Synuclein-alpha around the phosphorylation site of Tyr136. (avivasysbio.com)
  • Fluorescently-labeled monomeric, oligomeric and fibrillar species of alpha-synuclein were introduced into a donor cell population and co-cultured with an EGFP-expressing acceptor-cell population of differentiated neuron-like cells. (diva-portal.org)
  • We could confirm cell-to-cell transfer of all three alpha-synuclein species investigated. (diva-portal.org)
  • Alpha-Synuclein is known to reduce the fibrillization of the microtubule-associated protein, tau, to bind various targets such as 14-3-3, protein kinase C, synphilin-1, Elk and Tat-binding protein 1. (thermofisher.com)
  • a-synuclein may be involved in the regulation of dopamine release and transport and also may function to induce fibrillization of microtubule-associated protein tau. (acris-antibodies.com)