Beta synuclein. Medical search

A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.

A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.

A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.

A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.

A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)

A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.

Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.

A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.

Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act.

Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.

One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.

An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.

An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.

A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.

An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.

Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.

This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.

Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.

A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.

Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.

An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.

A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.

A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.

A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.

Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)

A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.

A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.

Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.

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.

Established cell cultures that have the potential to propagate indefinitely.

A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.

A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.

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)

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1% of the population over the age of 60. It is more common in men than women and has a higher incidence in Caucasians than in other ethnic groups.

The primary symptoms of Parkinson's disease are:

* Tremors or trembling, typically starting on one side of the body
* Rigidity or stiffness, causing difficulty with movement
* Bradykinesia or slowness of movement, including a decrease in spontaneous movements such as blinking or smiling
* Postural instability, leading to falls or difficulty with balance

As the disease progresses, symptoms can include:

* Difficulty with walking, gait changes, and freezing episodes
* Dry mouth, constipation, and other non-motor symptoms
* Cognitive changes, such as dementia, memory loss, and confusion
* Sleep disturbances, including REM sleep behavior disorder
* Depression, anxiety, and other psychiatric symptoms

The exact cause of Parkinson's disease is not known, but it is believed to involve a combination of genetic and environmental factors. The disease is associated with the degradation of dopamine-producing neurons in the substantia nigra, leading to a deficiency of dopamine in the brain. This deficiency disrupts the normal functioning of the basal ganglia, a group of structures involved in movement control, leading to the characteristic symptoms of the disease.

There is no cure for Parkinson's disease, but various treatments are available to manage its symptoms. These include:

* Medications such as dopaminergic agents (e.g., levodopa) and dopamine agonists to replace lost dopamine and improve motor function
* Deep brain stimulation, a surgical procedure that involves implanting an electrode in the brain to deliver electrical impulses to specific areas of the brain
* Physical therapy to improve mobility and balance
* Speech therapy to improve communication and swallowing difficulties
* Occupational therapy to improve daily functioning

It is important for individuals with Parkinson's disease to work closely with their healthcare team to develop a personalized treatment plan that addresses their specific needs and improves their quality of life. With appropriate treatment and support, many people with Parkinson's disease are able to manage their symptoms and maintain a good level of independence for several years after diagnosis.

The most common Parkinsonian disorder is Parkinson's disease, which affects approximately 1% of the population over the age of 60. Other Parkinsonian disorders include:

1. Dystonia: A movement disorder that causes involuntary muscle contractions and spasms.
2. Huntington's disease: An inherited disorder that causes progressive damage to the brain, leading to movement, cognitive, and psychiatric problems.
3. Progressive supranuclear palsy (PSP): A rare degenerative disorder that affects movement, balance, and eye movements.
4. Multiple system atrophy (MSA): A rare degenerative disorder that affects the autonomic nervous system, leading to symptoms such as tremors, rigidity, and difficulty with movement and coordination.
5. Corticobasal degeneration: A rare progressive neurodegenerative disorder that affects movement, cognition, and behavior.

Parkinsonian disorders can be difficult to diagnose, as the symptoms can be similar to other conditions such as essential tremor or dystonia. However, certain features can help distinguish one condition from another. For example, Parkinson's disease is characterized by a characteristic resting tremor, bradykinesia, and rigidity, while dystonia is characterized by sustained or intermittent muscle contractions that can cause abnormal postures or movements.

There is no cure for Parkinsonian disorders, but various medications and therapies can help manage the symptoms. These may include dopaminergic drugs to replace lost dopamine, muscle relaxants to reduce rigidity, and physical therapy to improve movement and coordination. In some cases, surgery may be recommended to regulate abnormal brain activity or to implant a deep brain stimulator to deliver electrical impulses to specific areas of the brain.

Overall, Parkinsonian disorders can have a significant impact on quality of life, but with proper diagnosis and treatment, many people are able to manage their symptoms and maintain their independence.

Examples of Impulse Control Disorders include:

1. Intermittent Explosive Disorder (IED): recurring episodes of sudden, violent, and aggressive outbursts, often resulting in property damage or physical harm to oneself or others.
2. Kleptomania: recurring failure to resist the impulse to steal, despite negative consequences.
3. Pyromania: recurring failure to resist the impulse to set fires, leading to deliberate and purposeful burning of property.
4. Pathological Gambling: persistent and recurring preoccupation with gambling, often leading to financial, legal, or relationship problems.
5. Trichotillomania (TTM): recurring urge to pull one's own hair, resulting in noticeable hair loss.
6. Dermatillomania: recurring urge to pick at or scratch one's own skin, leading to skin damage and scarring.
7. Compulsive Sexual Behavior (CSB): recurring and persistent preoccupation with sexual behavior, often resulting in negative consequences such as relationship problems, financial difficulties, or legal issues.

Treatment for Impulse Control Disorders often involves a combination of psychotherapy and medication. Cognitive-behavioral therapy (CBT) and habit reversal training are common therapeutic approaches used to help individuals identify and manage triggers, develop coping skills, and reduce the frequency and intensity of their compulsive behaviors. Medications such as selective serotonin reuptake inhibitors (SSRIs) may be prescribed to help reduce symptoms of anxiety or depression that may accompany ICDs.

It is important to note that while these disorders share some common features, they are distinct from one another and require individualized diagnosis and treatment.

Some common examples of neurodegenerative diseases include:

1. Alzheimer's disease: A progressive loss of cognitive function, memory, and thinking skills that is the most common form of dementia.
2. Parkinson's disease: A disorder that affects movement, balance, and coordination, causing tremors, rigidity, and difficulty with walking.
3. Huntington's disease: An inherited condition that causes progressive loss of cognitive, motor, and psychiatric functions.
4. Amyotrophic lateral sclerosis (ALS): A disease that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness, paralysis, and eventually death.
5. Prion diseases: A group of rare and fatal disorders caused by misfolded proteins in the brain, leading to neurodegeneration and death.
6. Creutzfeldt-Jakob disease: A rare, degenerative, and fatal brain disorder caused by an abnormal form of a protein called a prion.
7. Frontotemporal dementia: A group of diseases that affect the front and temporal lobes of the brain, leading to changes in personality, behavior, and language.

Neurodegenerative diseases can be caused by a variety of factors, including genetics, age, lifestyle, and environmental factors. They are typically diagnosed through a combination of medical history, physical examination, laboratory tests, and imaging studies. Treatment options for neurodegenerative diseases vary depending on the specific condition and its underlying causes, but may include medications, therapy, and lifestyle changes.

Preventing or slowing the progression of neurodegenerative diseases is a major focus of current research, with various potential therapeutic strategies being explored, such as:

1. Stem cell therapies: Using stem cells to replace damaged neurons and restore brain function.
2. Gene therapies: Replacing or editing genes that are linked to neurodegenerative diseases.
3. Small molecule therapies: Developing small molecules that can slow or prevent the progression of neurodegenerative diseases.
4. Immunotherapies: Harnessing the immune system to combat neurodegenerative diseases.
5. Lifestyle interventions: Promoting healthy lifestyle choices, such as regular exercise and a balanced diet, to reduce the risk of developing neurodegenerative diseases.

In conclusion, neurodegenerative diseases are a complex and diverse group of disorders that can have a profound impact on individuals and society. While there is currently no cure for these conditions, research is providing new insights into their causes and potential treatments. By continuing to invest in research and developing innovative therapeutic strategies, we can work towards improving the lives of those affected by neurodegenerative diseases and ultimately finding a cure.

... 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 ...

https://en.wikipedia.org/wiki/Beta-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 ... SYNUCLEIN , Definition of SYNUCLEIN by Oxford Dictionary on Lexico.com Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A ... All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid- ...

https://en.wikipedia.org/wiki/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 ...

https://en.wikipedia.org/wiki/Gamma-synuclein

September 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, ... and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.M111.243907. PMC 3190826. PMID ...

https://en.wikipedia.org/wiki/BEND2_(protein)

"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 ...

https://en.wikipedia.org/wiki/SNCAIP

... beta-amyloid, and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.M111.243907. PMC ... C6orf201 has a conserved alpha helix and a conserved beta strand in the protein. C6orf201 interacts with SRPK1, TMEM106B, and ...

https://en.wikipedia.org/wiki/C6orf201

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

https://en.wikipedia.org/wiki/Ccdc60

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

https://en.wikipedia.org/wiki/C11orf52

... beta-amyloid, and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-100. doi:10.1074/jbc.m111.243907. PMC ... CFAP299 protein is believed to interact with amyloid beta (A4) precursor protein (APP) and BCL2-associated athanogene 3 (BCL2 ...

https://en.wikipedia.org/wiki/CFAP299

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. PMC 3190826. PMID ... 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". ...

https://en.wikipedia.org/wiki/KIAA0825

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

https://en.wikipedia.org/wiki/C7orf31

... beta-amyloid, and alpha-synuclein". J. Biol. Chem. (39th ed.). 286 (39): 34088-34100. doi:10.1074/jbc.m111.243907. PMC 3190826 ... Prychitko TM, Moore WS (2000). "Comparative evolution of the mitochondrial cytochrome b gene and nuclear beta-fibrinogen intron ... amyloid beta (A4) precursor protein) through reconstituted complex. DUF4602 (PF15375) is generally 120+ amino acids long. There ... The secondary structure of these proteins primarily consist of alpha helices and coils with a small percentage of beta strands ...

https://en.wikipedia.org/wiki/C1orf131

September 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, ... and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088-34100. doi:10.1074/jbc.M111.243907. PMC 3190826. ...

https://en.wikipedia.org/wiki/C11orf53

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, ...

https://en.wikipedia.org/wiki/DMAC1

The Lashuel lab demonstrated that fibril growth and seeding capacity are key determinants of amyloid-beta- and alpha-synuclein- ... including alpha-synuclein, Tau and several N-terminal fragments of the Huntingtin protein. In addition, in collaboration with ... "α-Synuclein, Especially the Parkinson's Disease-associated Mutants, Forms Pore-like Annular and Tubular Protofibrils". Journal ... synuclein-mediated apoptotic cell death". Cell Death & Differentiation. 22 (12): 2107-2122. doi:10.1038/cdd.2015.79. ISSN 1476- ...

https://en.wikipedia.org/wiki/Hilal_Lashuel

Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... 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 ... Plaques are made up of small peptides, typically 39-43 amino acids in length, called amyloid beta (also written as A-beta or Aβ ...

https://en.wikipedia.org/wiki/Neurodegenerative_disease

Beta-synuclein and P27 As it is translated, polypeptides exit the ribosome mostly as a random coil and folds into its native ... between the transient structure in the monomeric state and the aggregation propensities of α-synuclein and β-synuclein". ... such as the two alpha and two beta chains of hemoglobin. Proteins are frequently described as consisting of several structural ...

https://en.wikipedia.org/wiki/Protein_structure

Paraproteins Amyloid beta peptides Amylin Transthyretin Alpha-synuclein Prions Uromodulin ASC speck complex Myoglobin Heme ... cathepsin beta, proteases, and NLPR3 inflammasomes. Cells undergo cell death via three main mechanisms: nectoptosis via RIPK1, ... interleukin 1 beta, cytokines, kinins, lipid inflammatory mediators, complement system activation, vasodilation, an increase in ...

https://en.wikipedia.org/wiki/Crystallopathy

... as well as filaments of Amyloid beta from Alzheimer's disease, Alpha-synuclein from Multiple system atrophy and TMEM106B. ... "Structures of alpha-synuclein filaments from multiple system atrophy". Nature. 585: 464-469. doi:10.1038/s41586-020-2317-6. PMC ... "Cryo-EM Structures of Amyloid-beta 42 Filaments from Human Brain". Science. 375: 167-172. doi:10.1126/science.abm7285. PMC ...

https://en.wikipedia.org/wiki/Sjors_Scheres

... and reducing amyloid beta or alpha-synuclein accumulation. Therapies under study as of 2019 aim to reduce brain levels of alpha ... and Lewy bodies and neurites were found to be immunoreactive for alpha-synuclein. Thus, alpha-synuclein aggregation as the ... Rarely, mutations in SNCA, the gene for alpha-synuclein, or LRRK2, a gene for a kinase enzyme, can cause any of DLB, ... The role of alpha-synuclein deposits is unclear, because individuals with no signs of DLB have been found on autopsy to have ...

https://en.wikipedia.org/wiki/Dementia_with_Lewy_bodies

... of AD clinical trials of metal chaperones targeting metal-induced aggregation of beta-amyloid in AD and of alpha-synuclein and ... 1987). "The amyloid beta protein gene: cDNA cloning, mRNA distribution, and genetic linkage near the Alzheimer locus". Science ... Tanzi also discovered that beta-amyloid plays a functional role in the brain as an anti-microbial peptide, supporting a role ... Tanzi demonstrated a key role for zinc, copper, and iron in beta-amyloid deposition and Lewy body formation. This finding has ...

https://en.wikipedia.org/wiki/Rudolph_E._Tanzi

... 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: ...

https://en.wikipedia.org/wiki/Amyloid_beta

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. Treatments with ...

https://en.wikipedia.org/wiki/Neuroscience_of_aging

In patients with PD, alpha synuclein is cut by AEP into toxic chunks. Active AEP was found at increased levels and translocated ... In AD the plaques are composed of amyloid beta, intracellular neurofibrillary tangles and tau protein. The dysfunction of APP ...

https://en.wikipedia.org/wiki/Asparagine_endopeptidase

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 ... Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates ...

https://en.wikipedia.org/wiki/Alpha-synuclein

With his laboratory, he also conducted extensive research on the second pathogenic component, senile plaques of beta-amyloid (A ... Synuclein Mice (with Silke Nuber PhD, Alice Y. Nam BS, Molly M. Rajsombath BS, Haley Cirka Xiaoping Hronowski PhD, Junmin Wang ... Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies (with John B ... Amyloid beta-peptide is produced by cultured cells during normal metabolism: a reprise (2006) The ups and downs of Abeta (2006 ...

https://en.wikipedia.org/wiki/Dennis_J._Selkoe

Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein". Science. 349 (6248 ... "Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins". Proceedings of the ... Olanow CW, Brundin P (January 2013). "Parkinson's disease and alpha synuclein: is Parkinson's disease a prion-like disorder?". ... "Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism". Proceedings of the National ...

https://en.wikipedia.org/wiki/Prion

"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 ...

https://en.wikipedia.org/wiki/Vesicular_monoamine_transporter_2

Her research has also shown how alpha-synuclein protein builds up in neurons that connect cells in Dementia with Lewy Bodies, ... research has shown that the amyloid beta and tau proteins that cause neuropathological lesions in Alzheimer's disease, ...

https://en.wikipedia.org/wiki/Tara_Spires-Jones

Amyloid beta (Aβ) is a small protein, most often 40 or 42 amino acids in length, that is released from a longer parent protein ... Suh YH; Checler F (September 2002). "Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and ... In this state, they cause other proteins of the same type to adopt the same abnormal beta-sheet-rich structure. The misfolded ... To liberate Aβ, APP is sequentially cleaved by two enzymes: first, by beta secretase (or β-amyloid cleaving enzyme (BACE)) ...

https://en.wikipedia.org/wiki/Amyloid_plaques

Mutations of synuclein alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Excessive activity of the crinophagy form of autophagy in the insulin-producing beta cells of the pancreas could reduce the ... The Road to Alpha-Synuclein Oligomerization in PD". Parkinson's Disease. 2011: 693761. doi:10.4061/2011/693761. PMC 3026982. ...

https://en.wikipedia.org/wiki/Autophagy

... and by amyloid-beta senile plaques amyloid-beta senile plaques. Several genetic factors have been identified as contributing to ... miR-7 and miR-153 act to reduce alpha-synuclein levels (a hallmark of PD) but are reduced in PD brain. DNA methylation Neurons ... Chen KL, Wang SS, Yang YY, Yuan RY, Chen RM, Hu CJ (January 2009). "The epigenetic effects of amyloid-beta(1-40) on global DNA ... Histone marks alpha-synuclein, the protein encoded by SNCA, can associate with histones and prevent their acetylation in ...

https://en.wikipedia.org/wiki/Epigenetics_of_neurodegenerative_diseases

Li W, Lee MK (June 2005). "Antiapoptotic property of human alpha-synuclein in neuronal cell lines is associated with the ... "Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin ...

https://en.wikipedia.org/wiki/Neuroprotection

... and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions ... 2002). "alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling ... The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse ... RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. ...

https://en.wikipedia.org/wiki/MAPK8IP1

This gene encodes an accessory enzyme which participates in the beta-oxidation and metabolism of unsaturated fatty enoyl-CoA ... and alpha-synuclein in sporadic Parkinson's disease". Hum. Genet. 124 (1): 89-94. doi:10.1007/s00439-008-0525-5. PMID 18568448 ...

https://en.wikipedia.org/wiki/2,4-dienoyl-CoA_reductase_1

Pronin AN, Morris AJ, Surguchov A, Benovic JL (Aug 2000). "Synucleins are a novel class of substrates for G protein-coupled ... Hu LA, Chen W, Premont RT, Cong M, Lefkowitz RJ (Jan 2002). "G protein-coupled receptor kinase 5 regulates beta 1-adrenergic ... Rajagopal K, Whalen EJ, Violin JD, Stiber JA, Rosenberg PB, Premont RT, Coffman TM, Rockman HA, Lefkowitz RJ (2006). "Beta- ... "Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor ...

https://en.wikipedia.org/wiki/GRK5

... and amyloid-beta plaques are extracellular deposits of the amyloid-beta protein. Current thinking in AD pathology goes beyond ... in alpha-synuclein (α-Syn) aggregation and misfolding, a characteristic of Parkinson's disease pathology. If there is a balance ... Alzheimer's disease (AD) has historically been characterized by two major hallmarks: neurofibrillary tangles and amyloid-beta ... Current thought is that inflammatory cytokine-activated microglia cannot phagocytose amyloid-beta, which may contribute to ...

https://en.wikipedia.org/wiki/Neuroinflammation

The central role of a-synuclein has generated many models aiming to elucidate its contribution to the dysregulation of various ... Wu, MY; Hill, CS (March 2009). "Tgf-beta superfamily signaling in embryonic development and homeostasis". Developmental Cell. ...

https://en.wikipedia.org/wiki/Biochemical_cascade

... beta 2-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.S.A. 87 (11): 4120-4. Bibcode:1990PNAS...87.4120M. doi: ... "Mitochondrial Lipid Abnormality and Electron Transport Chain Impairment in Mice Lacking α-Synuclein". Mol Cell Biol. 25 (22): ... "Cardiolipin exposure on the outer mitochondrial membrane modulates α-synuclein". Nature Communications. 9 (1): 817. Bibcode: ... cholesterol side-chain cleavage Import protein into mitochondrial matrix Anticoagulant function Modulates α-synuclein - ...

https://en.wikipedia.org/wiki/Cardiolipin

November 2000). "Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's beta-amyloid peptide, ... Combined, these methods have provided 3D atomic structures of amyloid fibrils formed by amyloid β peptides, α-synuclein, tau, ... corresponding to the interstrand and stacking distances in beta sheets. The "stacks" of beta sheet are short and traverse the ... Nelson R, Sawaya MR, Balbirnie M, Madsen AØ, Riekel C, Grothe R, Eisenberg D (June 2005). "Structure of the cross-beta spine of ...

https://en.wikipedia.org/wiki/Amyloid

For example, Hsp70 overexpression in human neuroglioma cells transfected with mutant alpha-synuclein led to 50% less oligomeric ... because knock down of Hsp70 promoted A-beta toxicity, and Hsp70 was shown to promote tau stability, while Hsp70 levels are ... April 2008). "Formation of toxic oligomeric alpha-synuclein species in living cells". PLOS ONE. 3 (4): e1867. Bibcode:2008PLoSO ... alpha-synuclein species, pointing towards the possibility that increasing its expression could diminish the spread of ...

https://en.wikipedia.org/wiki/Hsp70

The KIAA1211L protein predicted secondary structure is composed of 50% alpha helixes, 8.9% beta sheets, and 17.9% turns. The ... KIAA1211L protein is also predicted to interact with Alpha-synuclein (SNCA), E3 Ubiquitin-Protein Ligase Mdm2 (MDM2), Serine/ ... Glycogen Synthase Kinase 3 Beta (GSK3B) GSK3B is a protein kinase that regulates transcription factors and microtubules. As ... "GSK3B - Glycogen synthase kinase-3 beta - Homo sapiens (Human) - GSK3B gene & protein". www.uniprot.org. Retrieved 2017-04-23. ...

https://en.wikipedia.org/wiki/KIAA1211L

... encoding protein Amyloid beta A4 precursor protein-binding family B member 3 APC: adenomatosis polyposis coli ARL15: encoding ... synuclein, alpha interacting protein (synphilin) SPEF2: Sperm flagellar protein 2 SPINK5: serine protease inhibitor Kazal-type ... beta) MCEF: transcription factor AF4/FMR2 family, member 4 MEF2C: Myocyte-specific enhancer factor 2C MEF2C-AS1: encoding ... beta polypeptide) HMGXB3: encoding protein HMG-box containing 3 IK: Protein Red IRX1: Iroquois-class homeodomain protein (human ...

https://en.wikipedia.org/wiki/Chromosome_5

CTD's disorganized structure can turn into a full fledged Amyloid-like Beta-sheet rich structure causing it to adopt prion-like ... and alpha-synuclein-negative frontotemporal dementia (FTLD-TDP, previously referred to as FTLD-U) and in amyotrophic lateral ...

https://en.wikipedia.org/wiki/TAR_DNA-binding_protein_43

ISBN 978-0-470-97853-5. Wang, Hao; Kulas, Joshua A.; Ferris, Heather A.; Hansen, Scott B. (2020-10-14). "Regulation of beta- ... Also, FABP proteins have recently been shown to interact with a protein called synuclein to cause mitochondrial damage. ... Cheng, A (2021). "Impact of fatty acid-binding proteins in α-Synuclein-induced mitochondrial injury in synucleinopathy". ... December 2017). "Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes". The Journal of Neuroscience. 37 ...

https://en.wikipedia.org/wiki/Astrocyte

amyloid protein The hypothesis that beta amyloid protein is key to IBM has been supported in a mouse model using an Aβ vaccine ... and β-synuclein in skeletal muscle. ... active immunization markedly reduces intracellular Aβ deposits and attenuates the motor ... One review discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury." Dalakas (2006) suggested ...

https://en.wikipedia.org/wiki/Inclusion_body_myositis

Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the ... Payton JE, Perrin RJ, Clayton DF, George JM (November 2001). "Protein-protein interactions of alpha-synuclein in brain ... There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and ... Specifically, microtubules are composed of a heterodimer of alpha and beta-tubulin molecules. Cowan et al. demonstrated that b ...

https://en.wikipedia.org/wiki/Tubulin_alpha-1A_chain

Their lead compound, LMTX, targets aggregation of tau and is believed to act on synuclein, TDP-43 and huntingtin protein. Its ... ISBN 978-90-5702-173-2. Wischik CM, Wischik DJ, Storey JM, Harrington CR (2010). "Beta-Amyloid, Tau Protein and Glucose ...

https://en.wikipedia.org/wiki/TauRx_Therapeutics

In these cases, the FD cells express FD-cell markers (e.g. CD21, CD23, CD35, clusterin, podoplanin, gamma-synuclein) and in >90 ... beta-catenin (22.9%), TP53 (22.7%), and ECSIT (19.3%). These genes regulate cell growth and survival. Other genes (e.g. JAK3, ...

https://en.wikipedia.org/wiki/Epstein–Barr_virus–associated_lymphoproliferative_diseases

Jin YH, Kim YJ, Kim DW, Baek KH, Kang BY, Yeo CY, Lee KY (Apr 2008). "Sirt2 interacts with 14-3-3 beta/gamma and down-regulates ... "Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease". Science. 317 (5837): 516-19. ...

https://en.wikipedia.org/wiki/Sirtuin_2

alpha-synuclein. 140. not understood. GenBank: NP_000336. beta-synuclein. 134. unknown. GenBank:NP_001001502. ... Some Trp-free proteins such as tau protein and synuclein are able to aggregate and form insoluble fibrils. The author focused ... The product of tryptamine degradation IAA (synonyms: beta-Indolylacetic acid, indolylacetic acid) is also a TrpRS inhibitor [46 ... beta-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and Aβ deposits similar in structure and density to ...

https://www.mdpi.com/2072-6643/10/4/410

The SNCB gene provides instructions for making a protein called beta-synuclein. Learn about this gene and related health ... Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). ... A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. These ... beta-Synuclein suppresses both the initiation and amplification steps of alpha-synuclein aggregation via competitive binding to ...

https://medlineplus.gov/genetics/gene/sncb/

2020). Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimers disease. J. Neurol. Neurosurg. ... Nelson, T. J., and Alkon, D. L. (2007). Protection against beta-amyloid-induced apoptosis by peptides interacting with beta- ... 2018). The effect of beta-amyloid peptides and main stress protein HSP70 on human SH-SY5Y neuroblastoma proteome. Mol. Biol. 52 ... Aoki, M., Volkmann, I., Tjernberg, L. O., Winblad, B., and Bogdanovic, N. (2008). Amyloid beta-peptide levels in laser capture ...

https://www.proquest.com/openview/49d1d9780275f08d9bbed7ae41e02c9a/1?cbl=4424411&loginDisplay=true&loginDisplay=true&pq-origsite=gscholar

RNA Polymerase beta Prime RNA Polymerase II RNA Polymerase II RPB1 RNA Polymerase TFIIB SNAP-25 STAT3 Syntrophin Synuclein- ... beta-Amyloid 1-11 beta-Amyloid 1-16 beta-Amyloid 1-40 beta-Amyloid 17-24 Cadherin 11 CCL2 CD5 CD8a CD8b CD11c CD19 CD28 CD31 ... Hsp90alpha/beta I-Ak IGBP-1 IL-2 IL-3 IL-4 IL-34 Ly6K Mac-2 mCherry M-CSF NAC-1 Neurogranin NGAL NUP153 O-GlcNAc p120 Catenin ... α-Synuclein (2) Adaptor Proteins (4) Adhesion Molecules (221) APP/β-Amyloid (17) Autophagosome Markers (2) CD Molecules (479) ...

https://www.biolegend.com/nl-be/search-results?Applications=IP

Differential expression and distribution of alpha-, beta-, and gamma-synuclein in the developing human substantia nigra. Exp ... Axonal transport of synucleins is mediated by all rate components. Eur J Neurosci. 1999 Oct;11(10):3369-76. PubMed. ... Alpha-synuclein expression in the developing human brain. Pediatr Dev Pathol. 2004 Sep-Oct;7(5):506-16. PubMed. ... First, as pointed out previously, it has been shown that α-synuclein is present in the perikarya of fetal neurons (Galvin et al ...

https://www.alzforum.org/papers/neurons-derived-reprogrammed-fibroblasts-functionally-integrate-fetal-brain-and-improve

A number of proteins-including tau, alpha-synuclein, TDP-43, and amyloid-beta-are involved with various cellular processes. ... Disorders in which synuclein builds up inside neurons are called synucleinopathies. Changes in synuclein and/or its function ... Alpha-synuclein-The major protein present in abnormal clumps called Lewy bodies which are seen in the brains of people with ... Beta-amyloid plaques are also seen in some forms of LBD, cerebral amyloid angiopathy, and Parkinsons disease dementia. They ...

https://www.ninds.nih.gov/Disorders/All-Disorders/Dementia-Information-Page

Given the heterogeneity of both alpha-synuclein and beta-amyloid subspecies, applicants will be expected to focus on the use of ... In general, more work has been done to answer these questions for amyloid-beta aggregates than for alpha-synuclein aggregates, ... Since the structure of both alpha-synuclein and beta-amyloid are notably heterogeneous, applicants will be expected to focus on ... All centers will be expected to produce a publicly-available library of fully characterized alpha-synuclein and amyloid-beta ...

https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-19-013.html

https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-18-024.html

However, beta-amyloid did not differ between groups. This indicates that alpha-synuclein, phosphorylated tau, and IRS-1 play a ... The researchers measured the levels of alpha-synuclein, beta-amyloid, phosphorylated tau, and active IRS-1 proteins in each ... Extracellular vesicles originating from neurons have proteins such as alpha-synuclein, beta-amyloid, phosphorylated tau, and an ... Buildups of beta-amyloid and phosphorylated tau are typically associated with brain changes in Alzheimers disease but are also ...

https://www.nia.nih.gov/news/novel-blood-biomarkers-help-identify-cognitive-impairment-parkinsons-disease

beta-Synuclein Preferred Concept UI. M0159751. Registry Number. 0. Scope Note. A synuclein that is closely related to ALPHA- ... It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.. Terms. beta-Synuclein ... 2006; BETA-SYNUCLEIN was indexed under NERVE TISSUE PROTEINS 1988-2005. History Note. 2006(1988). Date Established. 2006/01/01 ... A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of ...

https://meshb.nlm.nih.gov/record/ui?ui=D051846

2003) Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma−/− knock-out mice. J Neurosci 23:8532-8538. ... 8 α-synuclein tg) or the antibody against α-synuclein (clone 274; 1 mg/ml) (n = 8 non-tg and n = 8 α-synuclein tg) into the ... 8 α-synuclein tg) or the mouse monoclonal antibody against α-synuclein (clone 274; 1 mg/ml) (n = 8 non-tg and n = 8 α-synuclein ... α-synuclein fibrils (0.2 μm) was pre-incubated with either 5 μg/ml of control IgG or antibodies against α-synuclein for 5 min ...

https://www.jneurosci.org/content/32/39/13454?ijkey=e704c7cb6709d15cfbfd9caea7e9e77785c043ed&keytype2=tf_ipsecsha

No significant incorporation of beta-synuclein into the fibrils was detected. The lack of fibrils formed by beta-synuclein is ... and gamma-synucleins, are also abundant in the brain. The synucleins are natively unfolded proteins. beta-Synuclein, which ... beta- And gamma-synucleins inhibit alpha-synuclein fibril formation. Complete inhibition of alpha-synuclein fibrillation was ... Biophysical properties of the synucleins and their propensities to fibrillate - Inhibition of alpha-synuclein assembly by beta ...

https://profiles.stanford.edu/sebastian-doniach

... and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol Pathol. (2):289-310. [Abstract ... and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol Pathol. (2):289-310.] ... Head injury, α-synuclein genetic variability and Parkinsons disease. Eur J Neurol. (5):874-8. [Abstract Lee PC, Bordelon Y, ... Head injury, α-synuclein genetic variability and Parkinsons disease. Eur J Neurol. (5):874-8.] ...

http://www.niehs.nih.gov/health/topics/conditions/parkinson/index.cfm

Metabolite-transporting beta-barrel ion channels reconstituted into planar lipid bilayers offer a useful model system for ... Voltage-activated complexation of alpha-synuclein with three diverse beta-barrel channels: VDAC, MspA, and alpha-hemolysin. ... Metabolite-transporting beta-barrel ion channels reconstituted into planar lipid bilayers offer a useful model system for ...

https://www.nichd.nih.gov/research/atNICHD/Investigators/Bezrukov/research/PolymersandSmallOsmolytes

Diabetes and cholesterol dyshomeostasis involve abnormal α-synuclein and amyloid beta transport in neurodegenerative diseases. ... Decreased brain 11[beta]-HSD1 expression following inflammation; a role in regulating brain energy homeostasis?. Verma, M., ...

https://research-repository.uwa.edu.au/en/publications/?ordering=type&showAdvanced=false&allConcepts=true&inferConcepts=true&publicationYear=2011&publicationYear=2012&publicationYear=2016&publicationYear=2019&publicationYear=2020&format=&descending=false&nofollow=true&page=2

MAM targeted several proteins networks including transport (e.g., alpha-synuclein), cytoskeletal (e.g., beta-tubulin, vimentin ... Immunochemistry confirmed several of the changes in protein expression (alpha-synuclein). Comparison with gene expression ...

https://tools.niehs.nih.gov/portfolio/index.cfm?do=portfolio.publicationDetail&id=135920

... amyloid beta peptide, alpha-synuclein) and associated toxicity. How these proteotoxic species form, the processes that ... amyloid beta peptide, alpha-synuclein) and associated toxicity. How these proteotoxic species form, the processes that ...

https://videocast.nih.gov/watch=5193

Levels of a protein found in the brain called alpha-synuclein (α-syn) are significantly lower than normal in cerebrospinal ... Additionally, trials ongoing or launching in the near future could use alpha-synuclein or beta-amyloid levels as exploratory ... Alpha-synucleins function in the brain is currently unknown but of great interest to Parkinsons researchers because it is a ... In addition to its presence in the brain, alpha-synuclein can be found in peripheral tissues and body fluids. The Movement ...

https://medicalxpress.com/news/2018-02-protein-spinal-fluid-posture-gait.html

Ligands targeting synaptic vesicle protein 2A (SV2A), alpha-synuclein (αSyn), and amyloid-beta (Aβ) are investigated.In paper I ...

https://www.avhandlingar.se/avhandling/8bd0cc38fb/

Region-specific beta-sheet conformation during alpha-synuclein aggregation revealed by segmental 13C-labeling and Raman ...

https://researchfestival.nih.gov/2018/concurrent-symposia-sessions

Protein Conformation, beta-Strand Actions. * Search in PubMed * Search in MeSH * Add to Search ... Taking a Bite Out of Amyloid: Mechanistic Insights into α-Synuclein Degradation by Cathepsin L Ryan P McGlinchey 1 , Gifty A ... Taking a Bite Out of Amyloid: Mechanistic Insights into α-Synuclein Degradation by Cathepsin L Ryan P McGlinchey et al. ... Cathepsin K is a potent disaggregase of α-synuclein fibrils. McGlinchey RP, Lacy SM, Walker RL 3rd, Lee JC. McGlinchey RP, et ...

https://www.ncbi.nlm.nih.gov/pubmed/?term=28614652

Commentary on Oeckl et al., "Serum Beta-Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181". Head, Elizabeth; ...

https://pesquisa.bvsalud.org/saudepublica/?lang=pt&q=au:Head,+Elizabeth

https://meshb-prev.nlm.nih.gov/record/ui?ui=D051846

... BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN ... β-Synuclein (β-syn) can counteract α-syn aggregation. Cross-breeding of β-syn transgenic mice with animals overexpressing α-syn ... alpha-Synuclein has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including ... The 140-amino-acid protein α-synuclein (α-syn) is the major constituent of Lewy bodies. The protein interacts with several ...

https://alzped.nia.nih.gov/node/7206/printable/print

author keywords: Pyrroloquinoline quinone trimethylester; alpha-synuclein; amyloid beta; blood-brain barrier permeability ...

https://ci.lib.ncsu.edu/units/127/citations?page=2&year=2018

Mouse mAbs are produced by hybrid cells formed by the fusion of mouse B cells and mouse myeloma cells

https://dshb.biology.uiowa.edu/monoclonal/mouse/custitem34/Avian,Turtle/custitem40/FFPE,Immunofluorescence

Association of cerebrospinal fluid beta-amyloid 1-42, T-tau, P-tau181, and alpha-synuclein levels with clinical features of ... Alpha-synuclein protein, tau protein, DJ-1 protein levels in CSF of all subjects were examined using Luminex assay according to ... The dysfunctional α-Synuclein has been implicated in a major mechanism in PD pathogenesis, oxidative stress might influence α- ... Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci U S A. 2009; 106:13052-13057. ...

https://www.oncotarget.com/article/6158/text/

... beta-Synuclein D12.776.641.860.625 D12.776.631.860.625 beta-Tocopherol D3.438.150.909.750.374 D3.633.100.150.909.750.374 ... beta-Lactams D4.75.80.875.99.221 D3.633.100.300 beta-Lipotropin D12.776.641.650.405.935.480 D12.776.631.650.405.935.480 beta- ... beta-Defensins D12.644.276.87.54 D12.776.467.87.188 D23.529.87.233 beta-Endorphin D12.776.641.650.405.935.239 D12.776.631.650. ... beta-Chain T-Cell Antigen Receptor G5.355.330.801.211 G5.344.801.211 G12.425.742.530.211 G12.500.287.211 G12.500.349.530.211 ...

https://decs.bvs.br/E/mnchg2017.txt

beta-Synuclein - Preferred Concept UI. M0159751. Scope note. A synuclein that is closely related to ALPHA-SYNUCLEIN. It may ... A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of ... beta-sinucleína. Scope note:. Sinucleína íntimamente relacionada con la ALFA-SINUCLEÍNA. Puede actuar como neuroprotector ... aggregated ALPHA-SYNUCLEIN.. Allowable Qualifiers:. AD administration & dosage. AE adverse effects. AG agonists. AI antagonists ...

https://decs.bvsalud.org/en/ths/resource/?id=51167

Under certain conditions, alpha-synuclein aggregates into oligomers that are gradually converted to the beta-sheet-rich ... Alpha-synuclein conformational changes and aggregation. Abnormally aggregated alpha-synuclein is the major component of Lewy ... SNCA multiplications lead to increased synthesis of alpha-synuclein and can cause Parkinson disease. Alpha-synuclein appears to ... Alpha-synuclein is a 140-amino-acid protein that is unfolded at neutral pH. However, when bound to membranes or vesicles ...

http://emedicine.medscape.com/article/1831191-overview

Synucleins are small soluble proteins expressed primarily in neural tissues and in certain tumors. (biolegend.com)
The family includes 3 known proteins, alpha synuclein, beta synuclein and gamma synuclein. (biolegend.com)
The alpha and beta synuclein proteins are found primarily in brain tissue, where they are seen mainly in pre-synaptic terminals. (biolegend.com)
7. Alpha-synuclein has structural and functional similarities to small heat shock proteins. (nih.gov)
11. Effects of novel peptides derived from the acidic tail of synuclein (ATS) on the aggregation and stability of fusion proteins. (nih.gov)
This FOA invites applications that will systematically and comprehensively characterize alpha-synuclein and amyloid-beta subspecies present in human Lewy Body Dementia (LBD) post-mortem brain tissue, identify toxic subspecies and potential mechanisms of toxicity, and characterize any interactions between the proteins that may contribute to increased toxicity and/or explain selective vulnerabilities of cells/circuits. (nih.gov)
2007). Indeed, this behavior is not unique for α-synuclein, as most presynaptic proteins tend to behave similarly in human brains (Galvin et al. (alzforum.org)
Extracellular vesicles originating from neurons have proteins such as alpha-synuclein, beta-amyloid, phosphorylated tau, and an insulin-signaling protein called Insulin Receptor Substrate 1 (IRS-1). (nih.gov)
The researchers measured the levels of alpha-synuclein, beta-amyloid, phosphorylated tau, and active IRS-1 proteins in each sample. (nih.gov)
For each, a hallmark of the disease is the appearance of misfolded and mutant proteins (Huntingtin, superoxide dismutase, amyloid beta peptide, alpha-synuclein) and associated toxicity. (nih.gov)
Besides β-synuclein, cellular proteins containing motifs resembling this sequence are potential CHK substrates. (edu.au)

IHC staining of anti-Synuclein-α/β, 130-140 antibody (clone Syn 202) on formalin-fixed paraffin-embedded human Parkinson's disease brain tissue. (biolegend.com)
Alpha synuclein is believed to be a major component of Lewy bodies in Parkinson's disease. (biolegend.com)
Mutations in alpha synuclein are associated with rare familial cases of early onset Parkinson's disease, Alzheimer's disease and several other neurodegenerative illnesses. (biolegend.com)
Conclusion Our study reveals a novel role for hemoglobin in α-synuclein post-translational modification and in dopamine neurons homeostasis suggesting neuronal hemoglobin is an important modifier in synucleinopathies such as Parkinson's disease. (biorxiv.org)
Altered expression and mutations in α-synuclein (α-syn) have been linked to Parkinson's disease (PD) and related disorders. (jneurosci.org)
Progressive accumulation of misfolded α-synuclein (α-syn) in cortical and subcortical brain regions has been proposed to play a central role in the pathogenesis of Parkinson's disease (PD) and Lewy body disease (LBD) ( Trojanowski and Lee, 1998 ). (jneurosci.org)
8. Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. (nih.gov)
12. Synucleins and their relationship to Parkinson's disease. (nih.gov)
13. Defective membrane interactions of familial Parkinson's disease mutant A30P alpha-synuclein. (nih.gov)
15. Aggregation of alpha-synuclein in the pathogenesis of Parkinson's disease. (nih.gov)
Alpha-synuclein buildup in the brain is a key pathological hallmark of Parkinson's and may also contribute to dementia. (nih.gov)
Buildups of beta-amyloid and phosphorylated tau are typically associated with brain changes in Alzheimer's disease but are also present in Parkinson's. (nih.gov)
Those with Parkinson's had less alpha-synuclein and IRS-1 and more phosphorylated tau than healthy individuals. (nih.gov)
Among those with Parkinson's, participants with normal cognition had more alpha-synuclein and IRS-1 and less phosphorylated tau than participants with cognitive impairment. (nih.gov)
This indicates that alpha-synuclein, phosphorylated tau, and IRS-1 play a role in the progression of Parkinson's with cognitive impairment. (nih.gov)
The results also seem to suggest that phosphorylated tau and alpha-synuclein are jointly involved in producing cognitive impairment in Parkinson's. (nih.gov)
Levels of a protein found in the brain called alpha-synuclein (α-syn) are significantly lower than normal in cerebrospinal fluid collected in Parkinson's disease patients suffering from postural instability and gait difficulty, a study led by movement disorders experts at Rush University Medical Center has found. (medicalxpress.com)
However, Parkinson's disease has been linked to some gene variants that affect how the immune system works, leading to an alternative theory that alpha-synuclein causes Parkinson's disease by triggering the immune system to attack the brain. (medicalxpress.com)
The study found that levels of alpha-synuclein were lower in cerebrospinal fluid from Parkinson's patients with certain motor function impairments - specifically in those who had more problems with balance and walking compared to those with more tremor. (medicalxpress.com)
In addition, levels of beta-amyloid, known for its association with Alzheimer's disease, were lower in those with Parkinson's and related to worse scores on a memory recall in Parkinson's as measured on a rest of thinking and memory given to study participants. (medicalxpress.com)
The study also showed that alpha-synuclein levels in plasma and saliva did not differ between people with Parkinson's and control volunteers, and alpha-synuclein did not significantly correlate among other biological fluids. (medicalxpress.com)
For example, people with Parkinson's and lower beta-amyloid may be more likely to develop memory problems and therefore would benefit more from a cognitive therapy," said Goldman. (medicalxpress.com)
in Parkinson's, it's α-synuclein. (nih.gov)

A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. (medlineplus.gov)
Beyer K, Domingo-Sabat M, Santos C, Tolosa E, Ferrer I, Ariza A. The decrease of beta-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies. (medlineplus.gov)
Beta-synuclein gene alterations in dementia with Lewy bodies. (medlineplus.gov)
The purpose of the Lewy Body Dementia Center Without Walls (CWOW) program is ultimately to understand how toxic species of alpha-synuclein and amyloid-beta produce the clinical pathology characteristic of Lewy Body Dementia. (nih.gov)
The 140-amino-acid protein α-synuclein (α-syn) is the major constituent of Lewy bodies. (nih.gov)

Mechanistically, it is demonstrated that miR-424(322)/503 targets gamma-Synuclein (SNCG), a factor that mediates this program rearrangement by controlling metabolic functions in fat cells, allowing adipocyte differentiation and adipose tissue enlargement. (helsinki.fi)

Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). (medlineplus.gov)
It is thought that this altered protein may not be able to prevent alpha-synuclein accumulation. (medlineplus.gov)
Though it may seem parsimonious to assume that the accumulation of α-synuclein in these grafts is due to the environment in which the grafts are, a closer inspection of the facts argue that the "accumulation" of α-synuclein seen in these grafted neurons may be related to the biology of the protein. (alzforum.org)
While progressive accumulation of amyloid beta protein (Abeta) oligomers has been identified as one of the central toxic events in AD, accumulation of alpha-synuclein (alpha-syn) resulting in the formation of oligomers and protofibrils has been linked to PD and Lewy body Disease (LBD). (nih.gov)

The SNCB gene provides instructions for making a protein called beta-synuclein. (medlineplus.gov)
Backgroud α-synuclein, a protein involved in the pathogenesis of several neurodegenerative disorders, is subjected to several post-translational modifications. (biorxiv.org)
α-synuclein (α-syn) is a 140-amino acid protein predominantly located at pre-synaptic terminals in association with synaptic vesicles. (biorxiv.org)
20. Role of protein-water interactions and electrostatics in alpha-synuclein fibril formation. (nih.gov)
Moreover, as Dr. Trojanowski points out, we do not know if such α-synuclein inclusions are necessarily permanent and direct evidence of PD, or simply a low-level dynamic shift in protein distribution and aggregation that may also occur in the normal brain. (alzforum.org)
α-synuclein is a normal protein with both cellular and synaptic distribution and function. (alzforum.org)
Ligands targeting synaptic vesicle protein 2A (SV2A), alpha-synuclein (αSyn), and amyloid-beta (Aβ) are investigated.In paper I, we compared synaptic density in transgenic AD and PD mouse models to their wild-type age-matched controls using SV2A PET. (avhandlingar.se)
Abstract: a-Synuclein is an intrinsically disordered protein of 140 residues that switches to an a- helical conformation upon binding phospholipid membranes. (nih.gov)
Messenger RNA (mRNA) transcripts [amyloid precursor protein, APP), α-synuclein (α-syn), Tau, neurofilament,light gene (NF-L), DJ-1/PARK7, Fractalkine and Neurosin] and long non-coding RNAs (RP11-462G22.1 and PCA3) were differentially expressed in CSF exosomes in PD and AD patients. (oncotarget.com)

Using an AAV9 we expressed α and β-chains of hemoglobin in dopamine neurons of Substantia Nigra pars compacta and evaluate its effect on α-synuclein post-translational modification, dopamine neurons survivals and behavioural outcome. (biorxiv.org)
the vast majority of dopamine neurons in each transplant case (containing many thousands of new dopamine neurons) do not have any α-synuclein aggregates, which I have personally studied with primary data and the same staining used in Mendez et al. (alzforum.org)
Even more misleading are the percentages of α-synuclein stained neurons in the Li et al. (alzforum.org)
Fagan correctly cites this on Alzforum: "In the patient with 12- and 16-year-old grafts, about 40 percent of TH-positive neurons contained detectable α-synuclein in the youngest graft, while about 80 percent of the cells were α-synuclein-positive in the older graft. (alzforum.org)
demonstrate that a small fraction of neurons contain α-synuclein stained inclusions. (alzforum.org)
However, the view that the presence of α-synuclein in these grafted neurons represents a "host to graft" disease progression needs further scrutiny. (alzforum.org)
First, as pointed out previously, it has been shown that α-synuclein is present in the perikarya of fetal neurons (Galvin et al. (alzforum.org)
The prevailing wisdom has been that these neurons may die from a toxic reaction to alpha-synuclein deposits. (medicalxpress.com)

2. Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity. (nih.gov)

Brown JW, Buell AK, Michaels TC, Meisl G, Carozza J, Flagmeier P, Vendruscolo M, Knowles TP, Dobson CM, Galvagnion C. beta-Synuclein suppresses both the initiation and amplification steps of alpha-synuclein aggregation via competitive binding to surfaces. (medlineplus.gov)
9. Structural transformation and aggregation of human alpha-synuclein in trifluoroethanol: non-amyloid component sequence is essential and beta-sheet formation is prerequisite to aggregation. (nih.gov)
10. Effects of nitration on the structure and aggregation of alpha-synuclein. (nih.gov)
β-Synuclein (β-syn) can counteract α-syn aggregation. (nih.gov)

18. Alpha-synuclein, Abeta and Alzheimer's disease. (nih.gov)
Cyclodextrin has also removed A-beta in Alzheimer's mice and provided neuroprotection - http://jem.rupress.org/content/209/13/2501.abstract . (nih.gov)

Using peptides derived from β-synuclein and positional scanning combinatorial peptide library screening, we defined the optimal substrate phosphorylation sequence recognized by the CHK active site to be E-x-[Φ/E/D]-Y-Φ-x-Φ, where Φ and x represent hydrophobic residues and any residue, respectively. (edu.au)

We showed in vivo in the brains of patients with AD/PD and in transgenic mice, Abeta and alpha-synuclein co-immunoprecipitate and form complexes. (nih.gov)

Syn 202 was raised using recombinant alpha and beta synucleins and recognizes residues 130-140 in alpha and beta synuclein. (biolegend.com)

Relationship of serum beta-synuclein with blood biomarkers and brain atrophy. (mpg.de)
Additionally, trials ongoing or launching in the near future could use alpha-synuclein or beta-amyloid levels as exploratory biomarkers in motor symptom or cognition drug trials, respectively. (medicalxpress.com)

In summary, so far all of our cases and Dr. Freed's seven cases up to 14 years after surgery have no signs of α-synuclein pathology. (alzforum.org)

It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN . (nih.gov)

Western blot of anti-Synuclein-α/β, 130-140 antibody (clone Syn 202). (biolegend.com)
Preclinical data have demonstrated binding of PRX012 to beta amyloid plaques and oligomers with high affinity, resulting in effective Aβ plaque occupancy and removal at relatively lower antibody concentrations, potentially enabling lower volumes of administration for subcutaneous delivery. (yahoo.com)
Adding TGF beta-neutralizing antibody restored the proliferation rate of CADASIL VSMCs. (helsinki.fi)
We assessed proliferation differences in the presence or absence of TGF beta-neutralizing antibody in ECs co-cultured with VSMCs. (helsinki.fi)

5. Degradation of wild-type alpha-synuclein by a molecular chaperone leads to reduced aggregate formation. (nih.gov)

3. Chaperone-like activities of alpha-synuclein: alpha-synuclein assists enzyme activities of esterases. (nih.gov)

National Institute of Diabetes and Digestive and Kidney study.13,14 a-Synuclein (aS) is a 140-residue IDP, Diseases, National Institutes of Health, Bethesda, MD 20892. (nih.gov)

In addition to its presence in the brain, alpha-synuclein can be found in peripheral tissues and body fluids. (medicalxpress.com)

Elucidate the normal and abnormal function of α-synuclein and its relationship to other PD genes (e.g. (nih.gov)

All synucleins have in common a highly conserved alpha helical lipid binding motif with similarity to the class-A2 lipid binding domains of the exchangeable apolipoproteins. (biolegend.com)
1. Structural changes in alpha-synuclein affect its chaperone-like activity in vitro. (nih.gov)
4. Beta-synuclein exhibits chaperone activity more efficiently than alpha-synuclein. (nih.gov)
17. Structural determinants of PLD2 inhibition by alpha-synuclein. (nih.gov)
All applications will be expected to include plans for developing a publicly-available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD. (nih.gov)
A synuclein that is closely related to ALPHA-SYNUCLEIN . (nih.gov)
alpha-Synuclein has been nominated as a potential target for AD. (nih.gov)

Metabolite-transporting beta-barrel ion channels reconstituted into planar lipid bilayers offer a useful model system for studying both polymer partitioning from multicomponent solutions and its osmotic action. (nih.gov)

However, beta-amyloid did not differ between groups. (nih.gov)

Results The over-expression of α and β-chains of hemoglobin in iMN9D dopamine cells increased C-terminal truncation of α-synuclein when cells were treated with α-synuclein preformed fibrils. (biorxiv.org)
By quantitative RT-PCR analysis, we observed increased Transforming growth factor-beta (TGF beta) gene expression in CADASIL VSMCs. (helsinki.fi)
We suggest that increased TGF beta expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature. (helsinki.fi)

Methods To assess the role of hemoglobin in α-synuclein post-translational modification and in dopamine cells physiology, we over-expressed α and β-chains of Hb in iMN9D dopamine cells to evaluate its effect on α-synuclein truncation. (biorxiv.org)

Our search revealed β-synuclein as a potential CHK substrate, and Y127 in β-synuclein as the preferential phosphorylation site. (edu.au)

Anatomy5

Organisms1

Diseases3

Chemicals and Drugs30

Psychiatry and Psychology1

Phenomena and Processes1

Information Science2

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

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

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

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

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

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

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

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

gamma-Synuclein

Synucleins

alpha-Synuclein

beta-Synuclein

Parkinson Disease

Protein D-Aspartate-L-Isoaspartate Methyltransferase

Lewy Bodies

Nerve Tissue Proteins

Parkinsonian Disorders

Impulse Control Disorders

Neurodegenerative Diseases

Dopamine

Interleukin-1beta

Neurons

Molecular Sequence Data

Amino Acid Sequence

beta 2-Microglobulin

Brain

Mice, Transgenic

Receptors, Adrenergic, beta

Integrin beta3

Transforming Growth Factor beta

Integrin alpha5beta1

Integrin beta4

Integrin alpha6beta4

Integrin beta Chains

beta 2-Glycoprotein I

Integrin alpha4beta1

Integrin alpha2beta1

Receptors, Adrenergic, beta-2

Integrins

Interleukin-1

Antigens, CD29

Integrin alpha6beta1

Receptors, Adrenergic, beta-1

Integrin alpha1beta1

Cells, Cultured

Cell Line

Glycogen Synthase Kinase 3

RNA, Messenger

Estrogen Receptor beta

Transforming Growth Factor beta1

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

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

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

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

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

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

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

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

Beta-synuclein

Synuclein

Gamma-synuclein

BEND2 (protein)

SNCAIP

C6orf201

Ccdc60

C11orf52

CFAP299

KIAA0825

C7orf31

C1orf131

C11orf53

DMAC1

Hilal Lashuel

Neurodegenerative disease

Protein structure

Crystallopathy

Sjors Scheres

Dementia with Lewy bodies

Rudolph E. Tanzi

Amyloid beta

Neuroscience of aging

Asparagine endopeptidase

Alpha-synuclein

Dennis J. Selkoe

Prion

Vesicular monoamine transporter 2

Tara Spires-Jones

Amyloid plaques