Alpha-synuclein messenger RNA (SNCA mRNA)

Alpha-synuclein messenger RNA (SNCA mRNA) is the primary transcript of the SNCA gene, which encodes the alpha-synuclein protein. This protein is a major component of Lewy bodies, the pathological hallmark of Parkinson's disease and other synucleinopathies (PubMed: 29453212). Under pathological conditions, increased expression or mutations in SNCA lead to the misfolding and toxic aggregation of the protein, contributing to neuronal death (NIH: Genetics Home Reference). Targeting the mRNA transcript allows for the reduction of total alpha-synuclein production at the source, potentially preventing the initiation of the aggregation cascade (PubMed: 31511311). Therapeutic strategies targeting SNCA mRNA primarily involve antisense oligonucleotides (ASOs) like BIIB101, which induce RNase H-mediated degradation of the transcript, or small molecules that target the mRNA's regulatory regions to inhibit translation (ClinicalTrials.gov: NCT04459988). While reducing alpha-synuclein levels is a promising neuroprotective strategy, researchers must monitor for potential adverse effects related to the loss of the protein's normal function in synaptic vesicle recycling and dopamine regulation (PubMed: 25239444). This target represents a precision medicine approach to slowing disease progression in patients with genetic predispositions or idiopathic Parkinson's disease.

Other names

SNCA mRNANACP mRNAPARK1 mRNAPARK4 mRNAAlpha-synuclein transcript

Antisense oligonucleotide-mediated RNase H degradation or RNA interference (RNAi) to reduce the translation of alpha-synuclein protein.