CDNF/MANF Review - PubMed
Pakarinen, Lindholm/PubMed/2023
Why It Matters
This caught my attention because it's one of the few neuroprotective strategies for Parkinson's that has actually made it to human testing. Most Parkinson's treatments just manage symptoms — they don't protect the neurons that are dying. CDNF works both as an external growth factor and inside cells to reduce ER stress, which might be why dopamine neurons die in the first place. But here's the reality check: safe doesn't mean effective yet, and we're still waiting for data showing it actually helps PD patients.
Key Findings
- CDNF and MANF both protected dopamine neurons and improved motor function in animal models of Parkinson's disease through neuroprotective and neurorestorative effects
- Phase I-II clinical trials in Parkinson's patients confirmed CDNF is safe and well-tolerated in humans, though efficacy data not yet reported
- These proteins work through two mechanisms: as extracellular trophic factors supporting neuron survival, and intracellularly by regulating the unfolded protein response to reduce ER stress
- Knockout animal studies revealed that removing CDNF or MANF disrupts normal dopamine system function, suggesting these proteins play important roles in maintaining healthy dopamine neurons
- ER stress, unfolded protein response dysfunction, and inflammation — all pathways that CDNF/MANF regulate — are implicated in Parkinson's disease development
Read the Paper↗PMID: 37555005