Autophagy-deficient neurons are neurons with impaired autophagic clearance mechanisms, leading to accumulation of damaged organelles, protein aggregates, and eventual neuronal death. This cell state is a key feature of most neurodegenerative diseases, where failed autophagy contributes to pathogenesis. [1][2]
| Pathway | Normal Function | Disease Effect |
|---|---|---|
| Macroautophagy | Aggregate clearance | Impaired in AD, PD, ALS |
| Mitophagy | Mitochondrial quality control | Lost in PD |
| Chaperone-mediated autophagy | Specific protein clearance | Declines with age |
| Microautophagy | Lysosomal uptake | Reduced activity |
Autophagy deficiency is observed across:
| Target | Approach | Stage |
|---|---|---|
| mTOR modulation | Rapamycin | Preclinical |
| MicroRNA modulators | miRNA targeting | Discovery |
| Lysosomal enhance | Gene therapy | Preclinical |