The Prion-Like Spreading of Alpha-Synuclein in Parkinson's Disease: Update on Models and Hypotheses
/MDPI/2026
Why It Matters
This caught my attention because it reframes Parkinson's as a spreading protein misfolding disease rather than isolated cell death. If alpha-synuclein really does spread cell-to-cell like prions do, it opens up intervention points—you might be able to block the spread mechanism itself, not just treat symptoms. The models reviewed here are helping researchers figure out which spreading pathways matter most, which could guide where to aim therapies. Not a doctor. Just a guy who reads the papers.
Key Findings
- Alpha-synuclein aggregates can transfer between neurons and seed new aggregation in recipient cells, demonstrated across multiple model systems
- The spreading pattern in experimental models mirrors the staged progression of Parkinson's pathology observed in human brains (Braak staging)
- Multiple cellular mechanisms may contribute to spread including direct cell-to-cell transfer, exosome release, and tunneling nanotubes
- Different alpha-synuclein strains show distinct spreading properties and pathology patterns, similar to prion strain variation
- The prion-like hypothesis remains contested with debate over whether spreading is the primary driver of disease progression or a secondary phenomenon