The α-synuclein proteostasis network and its translational applications in Parkinson's disease - PubMed
5 hours ago
- #alpha-synuclein
- #Parkinson's disease
- #proteostasis
- Parkinson's disease (PD) is characterized by mobility loss and muscle control issues, with α-synuclein (α-Syn) as a major component of Lewy pathology.
- The study delineated the α-Syn proteostasis network (PN) in the human substantia nigra, proposing a proteostasis activity score (PAS) to quantify α-Syn aggregation regulation.
- A PAS signature was identified, correlating with disease state, age-of-death in PD patients, and regional brain vulnerability to α-Syn aggregation.
- A transcriptome-derived network model was developed as a digital twin to prioritize PD therapeutic targets and facilitate drug repurposing.
- The study provides a computational framework for identifying and prioritizing therapeutic targets and repurposing candidates for PD.