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. Author manuscript; available in PMC: 2012 Jul 1.
Published in final edited form as: Neurobiol Dis. 2010 Jul 17;43(1):29–37. doi: 10.1016/j.nbd.2010.07.006

Figure 4. CMA and neurodegenerative disorders.

Figure 4

Schematic model of the evidence supporting connections between CMA function and three neurodegenerative disorders: Parkinson’s disease (PD), Tauopathies (TP) and Huntington’s disease (HD). PD: pathogenic synucleins interact abnormally with CMA components blocking degradation of other substrates. Aberrant interactions with CMA components have been described for UCHL-1. Reduced CMA activity in PD results in cytosolic accumulation of non functional MEF2D which decreases cell survival. TP: mutant forms of Tau undergo abnormal cleavage into amyloidogenic peptides. After a first cytosolic cut, the truncated protein is targeted to lysosomes via CMA, but fails to translocate. However, the part of Tau already in the lumen undergoes two additional cuts that generate the amyloidogenic peptides. HD: mutant forms of huntingtin (htt) have been successfully delivered to lysosomes via CMA for degradation by overexpression of a recombinant dimeric form of QBP1 with hsc70 binding sites.