MDPs in Neurodegeneration - Springer
Thakur et al./Springer/2025
Why It Matters
Mitochondrial dysfunction shows up early in neurodegeneration, and these naturally-occurring peptides encoded in mitochondrial DNA might offer protection. The concept is compelling—your mitochondria produce their own signaling molecules that could defend against brain diseases—but this is a review paper synthesizing existing research, not new clinical data. The practical takeaway: if you're tracking longevity interventions, MDPs are moving from "interesting biology" to "actual drug targets," though no therapies are available yet.
Key Findings
- Multiple mitochondrial-derived peptides including humanin, MOTS-c, and six small humanin-like peptides (SHLP1-6) have been identified as potential neuroprotective agents
- These peptides appear to work through multiple mechanisms: reducing oxidative stress, improving mitochondrial function, decreasing neuroinflammation, and preventing protein aggregation
- Humanin levels decline with age and in neurodegenerative disease states, suggesting a potential biomarker or therapeutic restoration target
- Evidence spans from cell culture to animal models showing protection against beta-amyloid toxicity, alpha-synuclein aggregation, and huntingtin protein damage
- The peptides are naturally encoded in mitochondrial DNA, representing an endogenous protective system rather than a foreign intervention