gamma-Synuclein: 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.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.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.beta-Synuclein: 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.Parkinson Disease: 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)Protein D-Aspartate-L-Isoaspartate Methyltransferase: 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.Lewy Bodies: 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.Nerve Tissue ProteinsParkinsonian Disorders: 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.Impulse Control Disorders: 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.Neurodegenerative Diseases: 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.Dopamine: 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.Interleukin-1beta: 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.Neurons: 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.Molecular Sequence Data: 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.Amino Acid Sequence: 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.beta 2-Microglobulin: 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.Brain: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Receptors, Adrenergic, beta: 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.Integrin beta3: 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.Transforming Growth Factor beta: 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.Integrin alpha5beta1: 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.Integrin beta4: 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.Integrin alpha6beta4: 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: 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.beta 2-Glycoprotein I: 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: 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.Integrin alpha2beta1: 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.Receptors, Adrenergic, beta-2: 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.Integrins: 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.Interleukin-1: 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.Antigens, CD29: 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)Integrin alpha6beta1: 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.Receptors, Adrenergic, beta-1: 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: 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.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Glycogen Synthase Kinase 3: 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, Messenger: 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.Estrogen Receptor beta: 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.Transforming Growth Factor beta1: 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.

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)

*SNCAIP

"Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta-galactosidase liquid assay". Neurosci. Lett. 325 (2 ... SNCAIP stands for "synuclein, alpha interacting protein" and can be signified by SNCAP_HUMAN, synphilin 1, synuclein, alpha ... "Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta-galactosidase liquid assay". Neurosci. Lett. 325 (2 ... "Entrez Gene: SNCAIP synuclein, alpha interacting protein (synphilin)". Neystat M, Rzhetskaya M, Kholodilov N, Burke RE (June ...

*C11orf52

... beta-amyloid, and alpha-synuclein". Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.M111.243907. PMC ...

*KIAA0825

Several programs suggest that the secondary structure of the protein is mainly helices with only a few beta sheets. Analysis of ... and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.M111.243907. PMID 21832049. ... The other is the Amyloid-beta precursor protein. This protein is an integral membrane protein found most commonly in the ... Bigelow HR, Petrey DS, Liu J, Przybylski D, Rost B (28 April 2004). "Predicting transmembrane beta-barrels in proteomes". ...

*C7orf31

... beta-amyloid, and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.m111.243907. PMC ...

*C1orf131

... beta-amyloid, and alpha-synuclein". J. Biol. Chem. (39th ed.). 286: 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 ...

*Tmem261

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, ...

*Neurodegeneration

Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin has been proved to be substrates of ... Plaques are made up of small peptides, 39-43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta- ... Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... in Alzheimer's disease are amyloid-beta and tau, in Parkinson's disease is alpha-synuclein and in Huntington's disease is ...

*Synuclein

... alpha-synuclein, beta-synuclein, and gamma-synuclein. Interest in the synuclein family began when alpha-synuclein was found to ... Alpha-synuclein InterPro: IPR002460 Beta-synuclein InterPro: IPR002461 Gamma-synuclein InterPro: IPR002462 Normal cellular ... All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid- ... Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors. ...

*Gamma-synuclein

... inhibition of alpha-synuclein assembly by beta- and gamma-synucleins". J. Biol. Chem. 277 (14): 11970-8. doi:10.1074/jbc. ... Gamma-synuclein is a protein that in humans is encoded by the SNCG gene. Synuclein-gamma is a member of the synuclein family of ... Gamma-synuclein is the least conserved of the synuclein proteins. Gamma-Synucleins expression in breast tumors is a marker for ... 1999). "Absence of mutation in the beta- and gamma-synuclein genes in familial autosomal dominant Parkinson's disease". DNA Res ...

*Beta-synuclein

... 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 ...

*Amyloid beta

... as has aggregation of alpha synuclein. While Aβ has been implicated in cancer development, prompting studies on a variety of ... Amyloid beta can be measured semiquantitatively with immunostaining, which also allows one to determine location. Amyloid beta ... By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to feature highly different conformational states ... Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ...

*Gap-43 protein

Synuclein. *Alpha-synuclein. *Beta-synuclein. *Gamma-synuclein. Other. *Agrin. *Chimerin. *Granin *Chromogranin A ...

*PCDHB13 - ويكيبيديا

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 ...

*CNOT6 - ويكيبيديا

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 ...

*SUB1 - ويكيبيديا، الموسوعة الحرة

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. ...

*NIPBL - ويكيبيديا، الموسوعة الحرة

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 ...

*MAP1B - ويكيبيديا

"Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments". J. Biol. Chem. ...

*PHF3 - ويكيبيديا، الموسوعة الحرة

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. ...

*MYO6 - ويكيبيديا

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. ...

*Neuroscience of aging

Another proposed mechanism for Alzheimer's is related to the accumulation of amyloid beta,. in a similar mechanism to the prion ... Similarly the protein alpha-synuclein is hypothesized to accumulate in Parkinson's and related diseases. Treatment of an age ...

*Neurodegeneration

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 ...

*Neurodegeneration

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 ...

*Prion

"α-Synuclein from Multiple System Atrophy Acts Like Prion in Mice". www.alzforum.org. 18 September 2015. [full citation needed] ... "Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins". Proceedings of the ... "Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism". Proceedings of the National ... is caused by a misfolded version of a protein called alpha-synuclein, and is therefore also classifiable as a prion disease. ...

*Alpha-synuclein

Beta amyloid Synuclein Contursi Terme - the village in Italy where a mutation in the α-synuclein gene led to a family history ... Therefore, NACP is now referred to as human alpha-synuclein. Alpha-synuclein is a synuclein protein of unknown function ... A single molecule study in 2008 suggests alpha-synuclein exists as a mix of unstructured, alpha-helix, and beta-sheet-rich ... The human alpha-synuclein protein is made of 140 amino acids and is encoded by the SNCA gene. An alpha-synuclein fragment, ...

*Vesicular monoamine transporter 2

"VMAT2 gene expression and function as it applies to imaging beta-cell mass". J. Mol. Med. 86 (1): 5-16. doi:10.1007/s00109-007- ... "Inhibition of vesicular monoamine transporter-2 activity in alpha-synuclein stably transfected SH-SY5Y cells". Cell. Mol. ... "Variation in the genes encoding vesicular monoamine transporter 2 and beta-1 adrenergic receptor and antidepressant treatment ...

*Epigenetics of neurodegenerative diseases

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 ...

*PDLIM1 - ويكيبيديا، الموسوعة الحرة

"Identification of a Wnt/Dvl/beta-Catenin --, Pitx2 pathway mediating cell-type-specific proliferation during development.". ...

*Chromosome 4 (human)

Beta-casein CXCL1: chemokine (C-X-C motif) ligand 1, scyb1 CXCL2: chemokine (C-X-C motif) ligand 2, scyb2 CXCL3: chemokine (C-X ... synuclein, alpha (non A4 component of amyloid precursor) SPATA5: Spermatogenesis-associated protein 5 STATH: gene with protein ... encoding protein Amyloid beta A4 precursor protein-binding family B member 2 ART3: encoding enzyme Ecto-ADP-ribosyltransferase ... Phosphatidylinositol 4-kinase type 2-beta PKD2: polycystic kidney disease 2 (autosomal dominant) PLK4: Serine/threonine-protein ...
... 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 ...
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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gamma-Synuclein Antibodies available through Novus Biologicals. Browse our gamma-Synuclein Antibody catalog backed by our Guarantee+.
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.
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
To comply with the National Institutes of Health (NIH) Public Access Policy, a PubMed Central reference number (PMCID) is required in NIH grant applications, proposals, and progress reports for any paper "authored by you or [arising] from your NIH funds (even if you are not an author)" (see http://publicaccess.nih.gov/FAQ.htm#c8).. One way to find the PMCID number is to use PubMed Centrals PMID: PMCID Converter available at http://www.ncbi.nlm.nih.gov/sites/pmctopmid. If you already have the PMID from a PubMed search (it may appear as the Accession Number in your EndNote library), the above converter will provide you with the corresponding PMCID to include in your grant. If you do not have the PMID number, you can look up a PMCID in PubMed. It will be listed in the lower right corner of the AbstractPlus view. A PMCID number will be assigned as soon as an article has successfully been submitted to PMC (see http://publicaccess.nih.gov/FAQ.htm#c9). If you have questions about the NIH Public Access ...
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.. ...
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. ...
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.
... , 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 ...
Gentaur molecular products has all kinds of products like :search , Assaypro \ gamma_Synuclein, anti_human IgG \ 12081-05011 for more molecular products just contact us
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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.. ...
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 (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 ...
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 ...
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购买我们的重组人alpha Synuclein (mutated E46 K)蛋白。Ab51188为全长蛋白,在大肠杆菌中生产并经过SDS-PAGE实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。
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
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。
Biochim Biophys Acta. 2014 Mar;1838(3):853-8. doi: 10.1016/j.bbamem.2013.11.016. Epub 2013 Dec 4.. Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy.. Zhang Z, Dai C, Bai J, Xu G, Liu M, Li C*.. Abstract. α-Synuclein is involved in Parkinsons disease and its interaction with cell membrane is crucial to its pathological and physiological functions. Membrane properties, such as curvature and lipid composition, have been shown to affect the interactions by various techniques, but ion effects on α-synuclein membrane interactions remain elusive. Ca(2+) dynamic fluctuation in neurons plays important roles in the onset of Parkinsons disease and its influx is considered as one of the reasons to cause cell death. Using solution Nuclear Magnetic Resonance (NMR) spectroscopy, here we show that Ca(2+) can modulate α-synuclein membrane interactions through competitive binding to anionic lipids, resulting in dissociation of α-synuclein from membranes. ...
My lab explores two related themes, those of synapse loss and neurodegeneration. Synapse loss is an early, defining event in neurodegenerative diseases, such as Parkinsons disease. In these prolonged diseases, decreases in synapse density are the best correlates of disease progression.Yet, little is known about the pathways that maintain synapses and their roles in aging and neurodegeneration. We are characterizing a novel presynaptic mechanism for the prevention of synapse loss and neurodegeneration involving the co-chaperone Cysteine String Protein alpha. This gene is also mutated in adult-onset neuronal ceroid lipofuscinosis, a neurodegenerative disorder with lysosomal pathology. We are also screening for new synapse maintenance genes using a dissociated neuronal culture system ...
Aggregation of α-synuclein can be promoted by the tubulin polymerization-promoting protein/p25α, which we have used here as a tool to study the role of autophagy in the clearance of α-synuclein. In NGF-differentiated PC12 catecholaminergic nerve cells, we show that de novo expressed p25...read more ...
Lewy bodies of a-synuclein protein are prominent characteristics in the Parkinsons disease (PD) pathology. The mechanism of Lewy body formation and consequent cytotoxicity was studied by Brandis et al. (2006) in a newly developed model organism of fission yeast. Though, the level of a-synuclein expression studied was either high or low, the wild-type and A53T familial mutant of a-synuclein followed the nucleation polymerization theory in the process of misfolding and aggregating. At high concentration, a-synuclein formed cytoplasmic aggregates in a concentration and time-dependent manner. However, these aggregates appeared to be independent of cytotoxicity. In this current study, the fission yeast model is used again but to evaluate a-synuclein misfolding, aggregation, and non-toxic properties when expression is moderate. The results indicate moderate a-synuclein expression to obey the nucleation polymerization model. In light of this study, a-synuclein aggregation requires a necessary threshold
2012 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no Suppl 1, S248-S249 p.Article in journal (Refereed) Published ...
Parkinsons disease (PD) is linked to impaired degradation and accumulation of the misfolded protein, alpha-synuclein. Therefore, accelerating the degradation of alpha-synuclein is of therapeutic interest. Our lab has tested the hypothesis that α-synuclein uses endocytosis as a route to the lysosome for its degradation. We have found evidence that several endocytosis genes regulate α-synucleins PD related properties. Most importantly, the absence of vps28 increases α-synuclein aggregation and cellular accumulation, and confers toxicity in a yeast PD model. I, specifically, found that increasing the concentration of α-synuclein in yeast that lack vps28 further enhances each of these pathological characteristics.
Non-steric-zipper models for pathogenic α-synuclein conformers. May 10, 2019 Related ArticlesNon-steric-zipper models for pathogenic α-synuclein conformers. APL Bioeng. 2018 Jun;2(2):026105 Authors: Schuman B, Won A, Brand-Arzamendi K, Koprich JB, Wen XY, Howson PA, Brotchie JM, Yip CM Abstract Parkinsons disease neurodegenerative brain tissue exhibits two biophysically distinct α-synuclein fiber isoforms-single stranded fibers that appear to be steric-zippers and double-stranded fibers with an undetermined structure. Herein, we describe a β-helical… ...
Objective/Rationale: Mounting evidence indicates a crucial role of pathological aggregates of the protein alpha-synuclein in Parkinsons disease (PD). Small aggregates termed oligomers seems to be toxic for nerve cells. Moreover, prion-like spread of pathological alpha-synuclein aggregation may cause progressive degeneration of brain areas. We recently developed the novel oligomer modulator anle138b that inhibits the formation of pathological alpha-synuclein oligomers and has shown therapeutic efficacy in several models of PD.Project Description:We will test anle138b in a novel, large PD model. First, we will test which doses are required to obtain relevant levels of anle138b in blood and tissue (
Pathogenic aggregation of α-Synuclein \(αSyn) is implicated in familial and sporadic Parkinson disease \(PD) and several other synucleinopathies. Choosing non-denaturing conditions, we developed a several purification schemes in order to obtain αSyn from human erythrocytes, enabling researchers ...
Our research focuses on the molecular basis of Parkinsons disease (PD). To achieve this, we study the cellular and molecular events by which mutations in genes linked to PD contribute to disease pathology. PD has been classically considered a sporadic disease, however, it is now recognized to have a substantial genetic component. Interestingly, the same genes involved in the autosomal-dominantly inherited forms of PD such as SNCA (α-synuclein), and LRRK2 can act as risk factors in sporadic PD, as well. Given the relevance of LRRK2 and α-synuclein with the sporadic forms of PD, our long-term research goal by interrogating a-synuclein and mainly LRRK2-dependent alterations at the cellular, network and behavioral levels is to understand the pathophysiology of PD. The gained knowledge will provide useful insights towards the development of mechanism-based therapeutic opportunities for a disease that is currently addressed symptomatically.. ...
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Karpinar, P.; Gajula Balija, M. B.; Kügler, S.; Opazo, F.; Rezaei-Ghaleh, N.; Wender, N.; Kim, H. Y.; Taschenberger, G.; Falkenburger, B. H.; Heise, H. et al.; Kumar, A.; Riedel, D.; Fichtner, L.; Voigt, A.; Braus, G. H.; Giller, K.; Becker, S.; Herzig, A.; Baldus, M.; Jäckle, H.; Eimer, S.; Schulz, J. B.; Griesinger, C.; Zweckstetter, M.: Pre-fibrillar α-synuclein variants with impaired bold β-structure increase neurotoxicity in Parkinsons disease models. EMBO Journal 28 (20), pp. 3256 - 3268 (2009 ...
|p|Description of the current state of knowledge of the pathogenesis of PD, including findings on autopsy, current genetics of PD, known risk factors for PD, and role of synuclein, mitochondrial function, etc.|/p| |p||em|Part of our Fundamentals course s
Wang G et al. (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein.. [^] ...
Previous studies revealed that pesticides interact with α-synuclein and accelerate the rate of fibrillation. These results are consistent with the prevailing hypothesis that the direct interaction of α-synuclein with pesticides is one of many suspected factors leading to α-synuclein fibrillation and ultimately to Parkinsons disease. In this study, the biophysical properties and fibrillation kinetics of α-synuclein in the presence of rotenone were investigated and, more specifically, the effects of rotenone on the early-stage misfolded forms of α-synuclein were considered. The thioflavine T (ThT) fluorescence assay studies provide evidence that early-phase misfolded α-synuclein forms are affected by rotenone and that the fibrillation process is accelerated. Further characterization by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) shows that rotenone increases the amount of ordered secondary structure in this intrinsically disordered protein. Morphological
α-synuclein is a small protein of 140 amino acids that is highly expressed in the brain. Its function remains poorly understood.10 Synucleinopathies are a group of neurodegenerative diseases associated with the abnormal accumulation of α-synuclein within cytoplasmic inclusions in neurons or oligodendroglia. These α-synuclein containing cytoplasmic aggregates occur throughout the brain, producing cell death and specific motor, autonomic and cognitive dysfunction in four phenotypically distinct synucleinopathies. When α-synuclein deposition occurs in neurons it aggregates into Lewy bodies, producing Parkinson disease (PD), dementia with Lewy bodies (DLB) or pure autonomic failure (PAF). Whereas in multiple system atrophy (MSA) neuronal death probably occurs as a consequence of α-synuclein aggregation in oligodendroglia.. A characteristic feature of the synucleinopathies is that they can all begin with varying degrees of autonomic dysfunction as the sole clinical feature - implying an initial ...
α-synuclein is a small protein of 140 amino acids that is highly expressed in the brain. Its function remains poorly understood.10 Synucleinopathies are a group of neurodegenerative diseases associated with the abnormal accumulation of α-synuclein within cytoplasmic inclusions in neurons or oligodendroglia. These α-synuclein containing cytoplasmic aggregates occur throughout the brain, producing cell death and specific motor, autonomic and cognitive dysfunction in four phenotypically distinct synucleinopathies. When α-synuclein deposition occurs in neurons it aggregates into Lewy bodies, producing Parkinson disease (PD), dementia with Lewy bodies (DLB) or pure autonomic failure (PAF). Whereas in multiple system atrophy (MSA) neuronal death probably occurs as a consequence of α-synuclein aggregation in oligodendroglia.. A characteristic feature of the synucleinopathies is that they can all begin with varying degrees of autonomic dysfunction as the sole clinical feature - implying an initial ...
TY - JOUR. T1 - Reduced expression of the G209A α-synuclein allele in familial parkinsonism. AU - Markopoulou, Katerina. AU - Wszolek, Zbigniew K.. AU - Pfeiffer, Ronald F.. AU - Chase, Bruce A. PY - 1999/9/13. Y1 - 1999/9/13. N2 - Missense mutations at the α-synuclein gene have been associated with familial parkinsonism. We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa-responsive parkinsonism maps to chromosomal region 4q21-23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the α-synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected ...
Dopamine and α-synuclein are a toxic combination for neurons, say Jin Xu, Bruce Yankner (Childrens Hospital, Boston, Massachusetts) and colleagues.. Aggregations of α-synuclein are a hallmark of Parkinsons disease (PD), and mutations in its gene are associated with familial forms of the disease. Yankner wanted to know why the protein is so toxic. When he overexpressed either wild-type or mutant forms of α-synuclein in cultured human dopaminergic neurons (DAN cells)-the cells affected in PD-a large number of the cells underwent apoptosis. In contrast, excess α-synuclein seemed to protect the nondopaminergic cortical neurons from apoptosis.. If endogenous synthesis of dopamine was blocked by the addition of a tyrosine hydroxylase inhibitor (THI), overexpression of α-synuclein no longer induced apoptosis. Thus, somehow, it is the combination of α-synuclein and dopamine that causes cell death, rather than overexpression of α-synuclein alone.. Yankner thinks the key to this ...
Toxicity of human alpha-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. Whether similar inhibition in mammals represents a cause of familial Parkinsons disease has not been established. We tested elements of this hypothesis by expressing human alpha-synuclein in mammalian kidney and neuroendocrine cells and assessing ER-to-Golgi transport. Overexpression of wild type or the familial disease-associated A53T mutant alpha-synuclein delayed transport by up to 50%; however, A53T inhibited more potently. The secretory delay occurred at low expression levels and was not accompanied by insoluble alpha-synuclein aggregates or mistargeting of transport machinery, suggesting a direct action of soluble alpha-synuclein on trafficking proteins. Co-overexpression of ER/Golgi arginine soluble N-ethylmaleimide-sensitive factor
Summary 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. The report provides comprehensive information
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The aggregation of α-synuclein (α-Syn) is believed to be one of the key steps driving the pathology of Parkinsons disease and related neurodegenerative disorders. One of the present hypotheses is that the onset of such pathologies is related to the rise of α-Syn levels above a critical concentration at which toxic oligomers or mature fibrils are formed. In the present study, we find that α-Syn aggregation in vitro is a spontaneous process arising at bulk concentrations as low as 1 nM and below in the presence of both hydrophilic glass surfaces and cell membrane mimicking supported lipid bilayers (SLBs). Using three-dimensional supercritical angle fluorescence (3D-SAF) microscopy, we observed the process of α-Syn aggregation in situ. As soon as α-Syn monomers were exposed to the surface, they started to adsorb and aggregate along the surface plane without a prior lag phase. However, at a ...
BACKGROUND: Activated microglia are a feature of the host response to neurodegeneration in Parkinsons disease (PD) and are thought to contribute to disease progression. Recent evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of PD and that this may be mediated by a microglial response. METHODS: We wished to discover whether the host response to eSNCA would be sufficient to induce significant cytokine production. In vitro cultured BV-2 microglia were used to determine the basic inflammatory response to eSNCA. In vivo, 8-week old Biozzi mice were subjected to a single intranigral injection of either 3 μg SNCA, lipopolysaccharide (LPS) or serum protein (BSA) and allowed to recover for 24 hours. A second cohort of animals were peripherally challenged with LPS (0.5 mg/kg) 6 hours prior to tissue collection. Inflammation was studied by quantitative real-time PCR for a number of pro-inflammatory genes and immunohistochemistry for microglial activation,
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The accumulation of clumps of the protein, alpha-synuclein, in the brain, in is considered to be the hallmark of Parkinsons disease
To observe the effects of Centella asiatica (C. asiatica) methanolic extract on α-synuclein aggregation and its expression in rotenone-exposed zebrafish. Zebrafish (Danio rerio) were exposed to 5 μg/L rotenone for 28 days and co-incubated with 2.5, 5.0 and 10.0 μg/mL of C. asiatica methanolic extract. The medium was changed every 48 h for maintain the concentration of rotenone and extract. After 28 days zebrafish were sacrificed on the ice block and protein was isolated from zebrafish brain for ELISA of dopamine and Western blotting of α-synuclein. Immunohistochemistry was conducted to observe the α-synuclein expressions from histopathological preparation of zebrafish brain. The head were soaked in 10% formaline for less than 24 h and embedded onto paraffin block, then sliced for immunohistochemistry using anti α-synuclein antibody. We also measured zebrafish motility for 5 min in each week. C. asiatica has important bioactive compounds such as asiaticoside that has anti-inflammatory and ...
Neuritic plaques comprised of amyloid ß (Aß) are one of the primary neuropathological hallmarks of Alzheimers disease (AD). However, Aß plaque deposition is preceded by aberrations of the endosomal/lysosomal system, including abnormally enlarged endosomal compartments, accumulation of protease-resistant proteins, and atypical activation of the lysosomal system. The functional mechanisms accounting for these abnormalities have not yet been delineated. Towards our goal of identifying the proteins whose dysfunction contributes to the development of endosomal/lysosomal pathology in AD, we have found that: 1) proteins implicated in regulating late endosomal trafficking are among the targets of oxidation (carbonylation) in the brain of a presenilin 1/amyloid precursor protein (PS1/APP) transgenic mouse model of AD; 2) reduced neuronal expression of synaptic membrane protein HNK-1/NCAM is associated with Aß pathology in models of Aß deposition in cell culture and an amyloid precursor protein ...
Neuritic plaques comprised of amyloid ß (Aß) are one of the primary neuropathological hallmarks of Alzheimers disease (AD). However, Aß plaque deposition is preceded by aberrations of the endosomal/lysosomal system, including abnormally enlarged endosomal compartments, accumulation of protease-resistant proteins, and atypical activation of the lysosomal system. The functional mechanisms accounting for these abnormalities have not yet been delineated. Towards our goal of identifying the proteins whose dysfunction contributes to the development of endosomal/lysosomal pathology in AD, we have found that: 1) proteins implicated in regulating late endosomal trafficking are among the targets of oxidation (carbonylation) in the brain of a presenilin 1/amyloid precursor protein (PS1/APP) transgenic mouse model of AD; 2) reduced neuronal expression of synaptic membrane protein HNK-1/NCAM is associated with Aß pathology in models of Aß deposition in cell culture and an amyloid precursor protein ...
Rashmi Chandra,1 Annie Hiniker,2 Yien-Ming Kuo,3 Robert L. Nussbaum,3,4 and Rodger A. Liddle1,5 First published June 15, 2017 - More info Abstract Parkinsons disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause…
AURORA, Colo. (Dec. 22, 2017) - While vigorous exercise on a treadmill has been shown to slow the progression of Parkinsons disease in patients, the molecular reasons behind it have remained a mystery.. But now scientists at the University of Colorado Anschutz Medical Campus may have an answer.. For the first time in a progressive, age-related mouse model of Parkinsons, researchers have shown that exercise on a running wheel can stop the accumulation of the neuronal protein alpha-synuclein in brain cells.. The work, published Friday in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate professor of medicine and Curt Freed, MD, professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.. The researchers said clumps of alpha-synuclein are believed to play a central role in the brain cell death associated with Parkinsons disease. The mice in the study, like humans, started to get Parkinsons symptoms in ...
1) 임상에서 사용되는 일반적 용량을 이용한 장기간 도파민 치료 시 대부분의 동물 및 인체 대상 연구에서 도파민 신경세포 소실의 가속화는 관찰되지 않았다[4,5]. 파킨슨병 치료의 메타분석에서도 도파민 치료를 받은 군이 그 어떤 사망이나 치명적 부작용의 발생이 높지 않았다[4].. 2) 15년 이상의 도파민 치료를 받은 파킨슨병 환자군의 사후(postmortem) 뇌 병리 연구에서 도파민 복용량과 뇌 내 레비소체(Lewy bodies) 침착 사이에 의미 있는 관련성은 발견되지 않았다[2].. 3) 도파민의 신경독성에 대한 거의 대부분의 보고는 생체 외(in vitro) 혹은 동물실험 등 실험실 연구가 주를 이루며, 생체 내(in vivo) 연구 근거는 뚜렷하게 보고된 바가 없다.. 레보도파의 조기 투여는 지연 치료보다 삶의 질을 향상시키고[6], 기저핵 내 손상된 도파민 회로를 최대한 생리적인 상태에 ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. 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. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. 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. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Poor sleep has been associated with the development of Alzheimers disease, and this has been thought to be in part because the protein amyloid beta increases with sleep deprivation. A new study explains more.. Experiments with mice show that sleep deprivation also rapidly increases levels of the other key Alzheimers disease protein, tau tangles.. The work built on findings that tau is high in older people who sleep poorly, and that, when people are kept awake all night, their tau levels rise by about 50%.. When mice had tau proteins seeded in the hippocampus of their brains, those who were kept awake for long periods each day (mice are nocturnal), showed significantly greater spread of tau tangles than those mice allowed to sleep normally. Moreover, the new tangles appeared in the same areas of the brain affected in people with Alzheimers.. Disrupted sleep also increased release of synuclein protein, a hallmark of Parkinsons disease. People with Parkinsons-like those with Alzheimers-often ...
The first author of the study is Shuchi Mittal, of Harvard Medical School, and the findings were published in the journal Science.. The research has several parts. First, the scientists conducted studies in cell cultures. Specifically, they searched for compounds that may downregulate the genetic expression of alpha-synuclein, which is the clumpy brain protein that builds up in excess and leads to Parkinsons symptoms. Using small molecule screening, the researchers found that a class of drugs called beta2-adrenoreceptor agonists has the potential to reduce alpha-synuclein expression. Then, they tested these drugs in mice and stem cells. The preliminary results suggested that two kinds of beta2-adrenergic drugs may have opposing effects on the risk of Parkinsons disease.. This prompted the team to further zoom in on these two types of beta2-adrenergic compounds: a beta2-adrenergic agonist called salbutamol (used for treating asthma), and beta2-adrenergic antagonists called beta-blockers (used ...
Huntingtons and Parkinsons diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingti
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AstraZeneca and Takeda Pharmaceutical Company Limited today announced that they have entered an agreement to jointly develop and commercialise MEDI1341, an alpha-synuclein antibody currently in development as a potential treatment for Parkinsons disease (PD). Alpha-synuclein (α-synuclein) is an aggregation-prone protein that contributes to the development of PD.
Introduction: Ianai Fishbein- Hot Topic Presenter "Altered Alpha Synuclein degradation and augmentation of Parkinson disease phenotype in a transgenic mouse model ...
Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of α-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell α-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether α-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood α-synuclein. We observed somewhat greater ...
Extracellular α-synuclein induces sphingosine 1-phosphate receptor subtype 1 uncoupled from inhibitory G-protein leaving β-arrestin signal intact. Zhang, L., Okada, T., Badawy, S., Hirai, C., Kajimoto, T., Nakamura, SI. Sci Rep. 7:44248 . doi:10.1038/srep44248 (2017). Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation. Okada, T., Hirai, C., Badawy, S., Zhang, L., Kajimoto, T., Nakamura, SI. Sci Rep. 6:37810. doi: 10.1038/srep37810 (2016). Sphingosine kinases modulate the secretion of amyloid β precursor protein from SH-SY5Y neuroblastoma cells: the role of α-synuclein.. Jesko, H., Okada, T., Strosznajder, RP., Nakamura, S.. Folia Neuropathol. 52(1), 70-78 (2014). Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. Kajimoto, T., Okada, T., Miya, S., Zhang, L., Nakamura, SI. Nat. Commun. 4:2712. doi:10.1038/ncomms3712 (2013). Regulation of synaptic strength by ...
Dementia with Lewy bodies is characterized by the accumulation of Lewy bodies and Lewy neurites in the CNS, both of which are composed mainly of aggregated α-synuclein phosphorylated at Ser129. Although phosphorylated α-synuclein is believed to exert toxic effects at the synapse in dementia with Lewy bodies and other α-synucleinopathies, direct evidence for the precise synaptic localization has been difficult to achieve due to the lack of adequate optical microscopic resolution to study human synapses. In the present study we applied array tomography, a microscopy technique that combines ultrathin sectioning of tissue with immunofluorescence allowing precise identification of small structures, to quantitatively investigate the synaptic phosphorylated α-synuclein pathology in dementia with Lewy bodies ...
The main findings of our study are that 1) expression of CSPalpha is reduced in degenerating forebrain in mild and severe Alzheimers disease. This downregulation occurs before synaptophysin levels drop. 2) CSPalpha expression is upregulated in Alzheimers disease cerebellum, a brain region protected from synaptic and neuronal loss in Alzheimers disease. This upregulation is at a level that occurs in young healthy cerebellum. 3) CSPalpha expression is not upregulated in FTLD cerebellum where neuropathology occurs. 4) In a mouse model of tauopathy CSPalpha upregulation inversely correlates with neurodegeneration. Taken together, these findings provide evidence that CSPalpha is a critical player of synaptic degeneration and synaptic survival in Alzheimers disease.. CSPalpha is a p25-regulated protein, and we have previously shown that p25 expression is downregulated in Alzheimers disease forebrain [6]. In addition, loss-of-function CSPalpha mutations cause adult-onset Kufs disease that is ...
Parkinsons disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)-containing intraneuronal inclusions-Lewy bodies (LBs) and Lewy neurites (LNs)-in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other brain regions. However, a cause-and-effect relationship between LB/LN formation and neurodegeneration remains unclear. Indeed, whether LB/LNs are toxic or represent a neuroprotective response has been contentious. Luk et al. (p. 949) injected α-Syn fibrils generated from recombinant mouse α-Syn protein into the dorsal striatum of wild-type mice and found that misfolded α-Syn caused the formation of PD-like LB/LNs and subsequent cell-to-cell transmission of pathologic α-Syn to anatomically interconnected regions, including the SNpc. Furthermore, the formation of LB/LNs and their accumulation in SNpc resulted in the progressive loss of these dopaminergic neurons, reduced dopamine innervations to ...
TY - JOUR. T1 - Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. AU - Wszolek, Zbigniew K. AU - Pfeiffer, R. F.. AU - Tsuboi, Y.. AU - Uitti, R. J.. AU - McComb, R. D.. AU - Stoessl, A. J.. AU - Strongosky, A. J.. AU - Zimprich, A.. AU - Müller-Myhsok, B.. AU - Farrer, M. J.. AU - Gasser, T.. AU - Calne, D. B.. AU - Dickson, Dennis W. PY - 2004/5/11. Y1 - 2004/5/11. N2 - Since the original 1995 report of a parkinsonian kindred, four individuals have been affected (mean age at onset, 65 years). All four had cardinal signs of Parkinson disease (PD) and good response to levodopa. Four autopsies showed neuronal loss and gliosis in the substantia nigra. Lewy bodies (LB) limited to brainstem nuclei were detected in one case, diffuse LB in the second, neurofibrillary tangles (NFT) without LB in the third, and neither NFT nor LB in the fourth. Genetic studies suggested linkage to the PARK8 locus on chromosome 12.. AB - Since the original 1995 report of a ...
Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinsons disease and Alzheimers disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein. MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinsons, and found that it can take on either of two proposed structures- floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinsons, says Dr. Collin Stultz, an associate professor of electrical engineering and computer science at MIT. "If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating," says Dr. Stultz, who is the senior author of a paper describing the ...
α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinsons disease and multiple system atrophy? Acta Neuropathologica February 2013 (epub) Aoife P. Kiely, Yasmine T Asi, Eleanna Kara, Patricia Limousin, Helen Ling, Patrick Lewis, Christos Proukakis,Niall Quinn, Andrew J. Lees, John Hardy, Tamas Revesz, Henry Houlden and Janice L. Holton a-Synucleinopathies share the common feature…
Mayo Clinic researchers have developed a method to reduce the production of alpha-synuclein in the brain. Alpha-synuclein is the protein which misfolds and creates Lewy bodies in the brains of people with Lewy body dementia and Parkinsons disease.. ...
Researchers from Brigham and Womens Hospital want to prevent alpha-synuclein from accumulating in the brain. To do so, the team searched for drugs that turn down alpha-synuclein production. They then tested the drugs in mice and stem cells and studied in data from the health records of millions of people living in Norway. The results of their efforts, which point to a new drug development path for PD, are published in Science.

Alpha-Synuclein Detection: ELISAs and AntibodiesAlpha-Synuclein Detection: ELISAs and Antibodies

Alpha-Synuclein Detection. Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult ... Alpha-synuclein (C‑terminus). 18671A, B. IHC. WB. Human. (S122). Rabbit IgG. Cross‑reacts with mouse and rat alpha-synuclein. ... ELISAs for Alpha-Synuclein Detection. The human alpha-synuclein assay kit (Cat. # 27740A) is a solid-phase sandwich ELISA using ... Antibodies for Alpha-Synuclein Detection. Anti-human alpha-synuclein antibody (Cat. # 18671A, B) is an affinity-purified IgG ...
more infohttp://www.clontech.com/US/Products/Cell_Biology_and_Epigenetics/Brain_and_CNS/Alpha-Synuclein?sitex=10020:22372:US&PEBCL1=7l5uwvG92P7mvnVVdfRJ5R3C3C&PEBCL1_pses=ZGE118626BB0E9861AA82736AC8AEF11AD56B05A5E18CCD6B4F2964846C4D03CBA7757FC0FA1326F25330AC51CAA304C3DDED0D21C7C0DBF1A

Alpha-Synuclein Detection: ELISAs and AntibodiesAlpha-Synuclein Detection: ELISAs and Antibodies

Alpha-Synuclein Detection. Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult ... Alpha-synuclein (C‑terminus). 18671A, B. IHC. WB. Human. (S122). Rabbit IgG. Cross‑reacts with mouse and rat alpha-synuclein. ... ELISAs for Alpha-Synuclein Detection. The human alpha-synuclein assay kit (Cat. # 27740A) is a solid-phase sandwich ELISA using ... Antibodies for Alpha-Synuclein Detection. Anti-human alpha-synuclein antibody (Cat. # 18671A, B) is an affinity-purified IgG ...
more infohttp://www.clontech.com/US/Products/Cell_Biology_and_Epigenetics/Brain_and_CNS/Alpha-Synuclein?sitex=10020:22372:US&PEBCL1=aIKusEIpMwYNK8PQyziG8j4QA5&PEBCL1_pses=ZG3F033B7EEC18F9BA45073BF6903C4F1EEB6153911982C0A4219ACD3AC5CFBF137D0B0BDF9283B8C1884D5D8BD7C9C2FC5238FCDA483F9B63

Alpha-synucleinAlpha-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 ...
more infohttps://pharos.nih.gov/idg/targets/P37840

Patients</span><span class=avia-menu-fx><span class=avia-arrow-wrap><span class=avia-arrow...Patients</span><span class="avia-menu-fx"><span class="avia-arrow-wrap"><span class="avia-arrow"...

... α-synuclein, β-synuclein, and ɣ-synuclein. The α- and β-synuclein proteins are found primarily in brain tissue. The ɣ-synuclein ... For example, the misfolding and aggregation of the amyloid beta (Aβ) peptide leads to a build-up of amyloid protein in the ... While the role synuclein proteins play in normal cellular functioning has not been fully determined, there are data to suggest ... In synucleinopathies, α-synuclein protein is believed to misfold and aggregate to form the protein structures that are thought ...
more infohttp://www.prothena.com/patients/

Beta-synuclein - WikipediaBeta-synuclein - Wikipedia

Beta-synuclein 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 ...
more infohttps://en.wikipedia.org/wiki/Beta-synuclein

Recombinant Human beta Synuclein protein (ab48853) ProtocolsRecombinant Human beta Synuclein protein (ab48853) Protocols

There are no specific protocols for Recombinant Human beta Synuclein protein (ab48853). Please download our general protocols ...
more infohttp://www.abcam.com/recombinant-human-beta-synuclein-protein-ab48853-protocols.html

Recombinant Anti-alpha + beta Synuclein antibody [EP1646Y] (ab51252)Recombinant Anti-alpha + beta Synuclein antibody [EP1646Y] (ab51252)

... beta Synuclein antibody [EP1646Y] validated for WB, Flow Cyt, ICC/IF and tested in Human, Mouse and Rat. Referenced in 10… ... The family includes 3 known proteins, alpha synuclein, beta synuclein and gamma synuclein. All synucleins have in common a ... Anti-alpha + beta Synuclein antibody [EP1646Y] - BSA and Azide free (ab189217) *Anti-alpha + beta Synuclein antibody [EP1646Y ... Anti-alpha + beta Synuclein antibody [EP1646Y] images. * Immunocytochemistry/ Immunofluorescence - Anti-alpha + beta Synuclein ...
more infohttp://www.abcam.com/alpha-beta-synuclein-antibody-ep1646y-ab51252.html

alpha/beta Synuclein 128002alpha/beta Synuclein 128002

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 ...
more infohttps://www.sysy.com/products/synuclein/facts-128002.php

Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACPAlpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP

... 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 ...
more infohttps://www.researchmoz.us/alpha-synuclein-non-a-beta-component-of-ad-amyloid-or-non-a4-component-of-amyloid-precursor-or-nacp-or-snca-pipeline-review-h2-2016-report.html

beta-Synuclein Recombinant Protein, Novus Biologicals | VWRbeta-Synuclein Recombinant Protein, Novus Biologicals | VWR

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- ...
more infohttps://us.vwr.com/store/product/9696487/beta-synuclein-protein-novus-biologicals

Recombinant Beta Amyloids, Taus, Synucleins & Peptides | rPeptideRecombinant Beta Amyloids, Taus, Synucleins & Peptides | rPeptide

We offer a large selection of Beta Amyloids, Taus, Synucleins, Calmodulins, Custom Products and more. ... 11.18.15 - IBTimes: Blue LED lights may help treat Alzheimers disease by suppressing beta-amyloid structure... , Beta Amyloids ... April 2016 - UKnowledge: VARIANCE OF THE AMYLOID BETA PEPTIDE AS A METRIC FOR THE DIAGNOSIS OF ALZHEIMERS DISEASE , Beta ... July 2015 - Annals of Neurology: Age and amyloid effects on human central nervous system amyloid-beta kinetics , Beta Amyloid ...
more infohttps://www.rpeptide.com/

FAQs:  Beta Amyloid Peptides, Tau Proteins, Synucleins | rPeptideFAQs: Beta Amyloid Peptides, Tau Proteins, Synucleins | rPeptide

Due to the fact that our beta-amyloids are recombinantly produced, there is a batch to batch consistency in the physical and ...
more infohttps://www.rpeptide.com/faqs/general

rPeptide - Synucleins, beta-amyloids, taus & antibodiesrPeptide - Synucleins, beta-amyloids, taus & antibodies

... 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, ...
more infohttps://www.lubio.ch/supplier/rpeptide/

SNCB gene - Genetics Home Reference - NIHSNCB gene - Genetics Home Reference - NIH

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, ...
more infohttps://ghr.nlm.nih.gov/gene/SNCB

Autophagy and apoptosis dysfunction in neurodegenerative disorders.  - PubMed - NCBIAutophagy and apoptosis dysfunction in neurodegenerative disorders. - PubMed - NCBI

... alpha-synuclein; amyloid beta precursor protein; amyloid-beta; amyotrophic lateral sclerosis; apolipo-protein E; apoptosis- ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=24211851

Furthermore to amyloid beta (A) and tau, -synuclein, most widely known | Beneficial Effects of RAF Inhibitor iFurthermore to amyloid beta (A) and tau, -synuclein, most widely known | Beneficial Effects of RAF Inhibitor i

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 ...
more infohttp://biodiversityhotspot.org/2017/07/furthermore-to-amyloid-beta-a-and-tau-synuclein-most-widely-known/

α-Synuclein | ALZFORUMα-Synuclein | ALZFORUM

to C-terminal aa 111-131 of human alpha synuclein. Specificity. alpha Synuclein; not beta synuclein ...
more infohttps://www.alzforum.org/antibodies/synuclein-23

Product - Page 2 of 13, Research Synaptic vesicles | Genetex Inc.Product - Page 2 of 13, Research 'Synaptic vesicles' | Genetex Inc.

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 ...
more infohttp://www.genetex.com/Web/search/Catalog/2?Research=0910

α-Synuclein | ALZFORUMα-Synuclein | ALZFORUM

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 ...
more infohttps://www.alzforum.org/antibodies/synuclein

Synucleins - Analytik Jena AGSynucleins - Analytik Jena AG

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 ...
more infohttps://www.analytik-jena.de/fr/life-science/products/products-dynamic/cat/antibodies-and-proteins/prod/synucleins.html

Synucleins - Analytik Jena AGSynucleins - Analytik Jena AG

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 ...
more infohttps://www.analytik-jena.de/ru/life-science/products/products-dynamic/cat/antibodies-and-proteins/prod/synucleins.html

alpha-Synuclein
     Summary Report | CureHunteralpha-Synuclein Summary Report | CureHunter

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 ...
more infohttp://www.curehunter.com/public/keywordSummaryD051844-alpha-Synuclein.do

Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading | PNASKinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading | PNAS

2000) Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc Natl Acad Sci ... 2009) Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ...
more infohttp://www.pnas.org/content/113/9/E1206.full

Frontiers | Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases |...Frontiers | Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases |...

... alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy ... alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy ... as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid ... as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid ...
more infohttps://www.frontiersin.org/articles/10.3389/fncel.2015.00124/full

JCI -
shRNA targeting α-synuclein prevents neurodegeneration in a Parkinsons disease modelJCI - shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson's disease model

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 ...
more infohttps://www.jci.org/articles/view/64502
  • 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)
  • Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification. (sysy.com)
  • Pathophysiological consequences of neuronal alpha-Synuclein overexpression: Impacts on ion homeostasis, stress signaling, mitochondrial integrity, and electrical activity. (mpg.de)
  • KLH-Conjugated synthetic peptide that included amino acid residues 80-96 of human α-synuclein. (biolegend.com)
  • A pH-dependent switch promotes beta-synuclein fibril formation via glutamate residues. (amedeo.com)
  • For the new strain, histidine hydrogen-deuterium mass spectrometry revealed altered packing arrangements of beta-sheets that encompass residues 139 and 186 of PrPSc. (diva-portal.org)