Role of α-synuclein in inducing innate and adaptive immunity in Parkinson disease - PMC
/PMC/2026
Why It Matters
This paper caught my attention because it challenges the old view that Parkinson's is purely a protein-folding problem. If immune activation is driving neurodegeneration, that opens up entirely different therapeutic angles — immunomodulation instead of just trying to clear misfolded proteins. For someone thinking about neuroprotection, this suggests inflammation control might matter more than we thought, though we're still early in understanding how to target this safely.
Key Findings
- Misfolded α-synuclein activates microglia (the brain's resident immune cells) and triggers inflammatory signaling cascades
- The protein can be presented as an antigen, triggering T-cell responses — meaning the adaptive immune system recognizes it as a threat
- Evidence suggests extracellular α-synuclein acts as a damage signal (DAMP), perpetuating chronic inflammation
- Peripheral immune cells can infiltrate the brain in Parkinson's, creating a systemic immune component beyond just local brain inflammation
- Nitrated and oxidized forms of α-synuclein appear particularly immunogenic — damage to the protein makes it more likely to trigger immune responses
Read the Paper↗PMC4405142