SNCA

GeneName

SNCA

Summary

SNCA, also known as Syn or alpha synuclein, is a 14 kDa protein predominantly expressed in the brain, particularly in presynaptic terminals of neurons. It is associated with the actin cytoskeleton and synaptic vesicles, playing a crucial role in neurotransmitter release and synaptic function. SNCA is involved in various cellular processes, including lipid binding, calcium ion binding, and interactions with microtubules. It is known for its propensity to form amyloid fibrils, which are implicated in neurodegenerative diseases such as Parkinson's disease. The protein is localised to multiple cellular compartments, including the cytoplasm, membrane, and mitochondria, and is involved in regulating synaptic transmission and neuronal plasticity.

Importance

SNCA is relevant to: - The pathogenesis of Parkinson's disease due to its aggregation into toxic forms that disrupt neuronal function - The regulation of synaptic transmission and plasticity, which are essential for learning and memory - The modulation of dopamine release, impacting motor control and behaviour - The response to oxidative stress and inflammation, linking it to various neurodegenerative conditions - The study of amyloid fibril formation, contributing to our understanding of protein misfolding diseases

Top Products

For researchers investigating SNCA, we recommend two excellent primary antibodies. The first is the well-cited Anti-Alpha-synuclein antibody [MJFR1] (ab138501), which has garnered 222 citations, highlighting its reliability in the field. This monoclonal antibody is validated for use in several applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). Notably, it has also been validated in knockout models, ensuring its effectiveness in various experimental setups.Additionally, we offer the recombinant antibody, Anti-Alpha-synuclein aggregate antibody [MJFR-14-6-4-2] - Conformation-Specific (ab209538). This product is particularly suited for IHC and ICC applications and has received 98 citations, demonstrating its growing acceptance in the research community. The recombinant nature of this antibody provides batch-to-batch consistency, making it an excellent choice for researchers seeking reliable detection of alpha-synuclein aggregates. The Anti-Alpha-synuclein antibody ELISA Kit (ab190376), supported by 3 citations, is an excellent option for researchers looking to measure SNCA levels with confidence.

Abcam Product Citation Summary

The data indicates a strong focus on the role of SNCA (alpha-synuclein) in various contexts, particularly in neurodegenerative studies involving human and mouse models. The use of multiple applications, including Western blotting and immunohistochemistry, highlights the importance of this protein in understanding its uptake, degradation, and interactions in conditions such as α-synuclein fibrillization and accumulation in microglia. The studies span a range of species, primarily focusing on human and mouse samples, suggesting a broad interest in the implications of SNCA in neurobiology.

Abcam Product Citation Table

Domain

The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments.

Function

Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:28288128, PubMed:30404828). Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Also acts as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590).

Involvement in disease

Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.

Parkinson disease 1, autosomal dominant

PARK1

A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.

None

The disease is caused by variants affecting the gene represented in this entry.

Parkinson disease 4, autosomal dominant

PARK4

A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.

None

The disease is caused by variants affecting the gene represented in this entry.

Dementia, Lewy body

DLB

A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress.

Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.

Ubiquitinated. The predominant conjugate is the diubiquitinated form.

Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.

Sequence Similarities

Belongs to the synuclein family.

Tissue Specificity

Highly expressed in presynaptic terminals in the central nervous system. Expressed principally in brain.

Cellular localization

• Cytoplasm
• Membrane
• Nucleus
• Synapse
• Secreted
• Cell projection
• Axon
• Membrane-bound in dopaminergic neurons (PubMed:15282274). Expressed and colocalized with SEPTIN4 in dopaminergic axon terminals, especially at the varicosities (By similarity).

Alternative names

NACP, PARK1, SNCA, Alpha-synuclein, Non-A beta component of AD amyloid, Non-A4 component of amyloid precursor

Database links

swissprot:P37840 swissprot:Q16143 entrezGene:6623 omim:163890 omim:602998 omim:602569 swissprot:O76070 entrezGene:6622 entrezGene:6620 swissprot:Q6FHG5