| First Author | Yang Q | Year | 2009 |
| Journal | Science | Volume | 323 |
| Issue | 5910 | Pages | 124-7 |
| PubMed ID | 19119233 | Mgi Jnum | J:143024 |
| Mgi Id | MGI:3822670 | Doi | 10.1126/science.1166088 |
| Citation | Yang Q, et al. (2009) Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323(5910):124-7 |
| abstractText | Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease. |
