Editors' ChoiceCell Biology

Chaperone to Neurodegeneration

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Sci. Signal.  06 Jan 2009:
Vol. 2, Issue 52, pp. ec8
DOI: 10.1126/scisignal.252ec8

Although autophagy in general is known to play a role in the process of neurodegeneration, it is not clear what role, if any, chaperone-mediated autophagy, which selectively regulates the levels of specific cytoplasmic proteins, plays in cellular survival and death. Members of the MEF2 (myocyte enhancer factor 2) family are nuclear transcription factors involved in neuronal survival, differentiation, and synaptic function. Now Yang et al. provide in vitro and in vivo data from knockout mice, transgenic mice, and human brains to show that chaperone-mediated autophagy directly targets MEF2 for lysosomal degradation. During the process, MEF2 is translocated from the nucleus to the cytoplasm. The chaperone-mediated autophagy of MEF2 is sensitive to the level of α-synuclein, increased levels of which can cause Parkinson's disease. Thus, chaperone-mediated autophagy can play a direct role in modulating the neuronal survival machinery and may be involved in the process by which mutant and/or overexpressed α-synuclein can undermine neuronal viability.

Q. Yang, H. She, M. Gearing, E. Colla, M. Lee, J. J. Shacka, Z. Mao, Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323, 124–127 (2009). [Abstract] [Full Text]