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Author Notes:

To whom correspondence should be addressed: Zixu Mao, zmao@pharm.emory.edu

We thank H. Rees and D. Cooper at Emory Neuroscience NINDS Core Facility (NS055077) and UAB Neuroscience Core Facility (NS47466 and NS57098) for assistance in imaging and immunohistochemistry analysis, and J. Blum and A. M. Cuervo for Hsc70 and Lamp2a constructs.


Research Funding:

Supported by NIH grants NS048254 (Z.M.), AG023695 (Z.M.), and NS038065 (M.L.) and by Emory and UAB Alzheimer’s Disease Research Center pilot grants (Z.M. and J.J.S.) and the Robert Woodruff Health Sciences Center Fund (Z.M.).

Regulation of Neuronal Survival Factor MEF2D by Chaperone-Mediated Autophagy


Journal Title:



Volume 323, Number 5910


, Pages 124-127

Type of Work:

Article | Post-print: After Peer Review


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 α-synuclein transgenic mice and patients with Parkinson’s disease. Wild-type α-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.

Copyright information:

© 2009 American Association for the Advancement of Science

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