SNCA

About SNCA

SNCA on chromosome 4q22.1 encodes alpha synuclein, a presynaptic neuronal protein involved in synaptic vesicle trafficking and neurotransmitter release. Misfolded alpha synuclein aggregates form Lewy bodies, the pathological hallmark of Parkinson disease and dementia with Lewy bodies, and glial inclusions in multiple system atrophy, conditions grouped together as synucleinopathies. Point mutations such as A53T, A30P, and E46K, as well as duplications and triplications of the gene, cause rare familial early onset Parkinson disease, and the triplications show that simply having more of the normal protein can cause disease. The A53T variant, reported in 1997, was found in the Contursi kindred, a large family of Italian origin, and was the first genetic cause of Parkinson disease identified. Alpha synuclein pathology appears to spread through connected neural circuits, a pattern described by the Braak staging scheme. Variants in GBA1 are an important genetic risk factor for Parkinson disease, linking lysosomal dysfunction to alpha synuclein accumulation. Seed amplification assays that detect misfolded alpha synuclein in spinal fluid are being developed as diagnostic biomarkers, and antibodies and aggregation inhibitors are under investigation.