Alpha-synuclein (SNCA) (SNCA)

Alpha-synuclein is a 140-amino acid protein primarily localized in the presynaptic terminals of neurons, where it plays a critical role in regulating synaptic vesicle trafficking and neurotransmitter release (UniProt P37840). In neurodegenerative disorders known as synucleinopathies, such as Parkinson's disease and Dementia with Lewy bodies, this protein undergoes a conformational change, misfolding into toxic oligomers and eventually forming insoluble aggregates called Lewy bodies (StatPearls, 2023). These Lewy bodies are the pathological hallmark of the disease and are associated with progressive neuronal dysfunction and cell death (PubMed, PMID: 31203786). Therapeutic strategies targeting alpha-synuclein include monoclonal antibodies designed to clear extracellular aggregates, small molecules that inhibit the aggregation process, and antisense oligonucleotides to reduce protein production (Roche, 2024). While the term "Lewy body" refers to the visible pathological inclusion, the alpha-synuclein protein itself is the primary molecular target for drug development (NIH, 2023). Monitoring treatment efficacy often involves seed amplification assays that detect misfolded protein species in cerebrospinal fluid (The Lancet Neurology, 2023).

Other names

Lewy bodyNon-amyloid component of plaque precursorNACPPARK1PARK4

Inhibition of alpha-synuclein aggregation, promotion of aggregate clearance via monoclonal antibodies, and reduction of protein synthesis using antisense oligonucleotides.