Alpha-synuclein (SNCA) mRNA (SNCA mRNA)

Alpha-synuclein (SNCA) is a presynaptic protein that plays a critical role in regulating synaptic vesicle trafficking and neurotransmitter release, particularly dopamine (UniProt P37840). In neurodegenerative disorders known as synucleinopathies, such as Parkinson's disease and Dementia with Lewy bodies, alpha-synuclein undergoes misfolding and aggregation into toxic Lewy bodies (Goedert et al., 2017). Targeting the translation of SNCA mRNA aims to reduce the overall production of the alpha-synuclein protein, thereby lowering the concentration of the monomeric form available for aggregation. Therapeutic approaches include antisense oligonucleotides (ASOs) that induce mRNA degradation and small molecules that bind to the 5' untranslated region (UTR) of the SNCA mRNA to inhibit ribosomal recruitment (Cole et al., 2021; Chen et al., 2022). By decreasing the protein burden, these strategies seek to slow or halt disease progression. However, maintaining a threshold level of functional alpha-synuclein is necessary to avoid disrupting normal synaptic function.

Other names

Alpha-synuclein translationSNCA translationAlpha-synuclein mRNANACPPARK1PARK4

Inhibition of protein synthesis through binding to the 5' untranslated region (UTR) of mRNA or through antisense oligonucleotide-mediated mRNA degradation.