alphasynucleine

Alpha-synuclein, also written as alpha-synuclein and abbreviated as α-synuclein, is a small protein primarily expressed in the brain. It is encoded by the SNCA gene and is especially abundant at presynaptic terminals of neurons. Its exact physiological role is not fully understood, but it is thought to participate in the regulation of synaptic vesicle trafficking and neurotransmitter release, particularly for dopamine, and to interact with lipid membranes.

The protein is considered natively unfolded in solution but adopts alpha-helical structures when attached to lipid membranes. A central non-amyloid component (NAC) region drives aggregation under certain conditions, leading to the formation of oligomers, protofibrils, and fibrils. Pathological α-synuclein aggregates accumulate in structures known as Lewy bodies and Lewy neurites, which are hallmark features of several neurodegenerative diseases. Post-translational modifications, including phosphorylation at Ser129, ubiquitination, and C- or N-terminal truncation, are associated with disease-related forms of the protein.

Genetically, alterations in SNCA can influence disease risk. Mutations such as A53T, A30P, and E46K, as well as gene multiplications (duplications or triplications), cause familial Parkinson’s disease or related disorders. In addition, α-synuclein aggregation and spread appear to contribute to sporadic Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, where misfolded α-synuclein can propagate in a prion-like manner between cells.

Research into α-synuclein includes exploring its normal function, mechanisms of aggregation, and strategies to reduce pathology. Therapeutic approaches under investigation encompass immunotherapies, aggregation inhibitors, and gene-silencing techniques, alongside biomarker and imaging studies to monitor disease progression.