. Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain. J Neurosci. 2012 May 30;32(22):7585-93. PubMed.

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  1. The new paper from Zhenyu Yue is very interesting, and certainly further implicates autophagy as a step involved in Parkinson's pathogenesis. This seems to provide support for other work from Richard Youle's (Narendra et al., 2010) and Charleen Chu's (Dagda et al., 2009) labs suggesting that a deficit in mitochondrial turnover by macroautophagy might occur with the parkin and PINK mutations that can cause some cases of PD. So, a mutation that directly affects macroautophagy may model a downstream step in PD. One possibility is that mutant α-synuclein first disturbs another form of autophagy, known as chaperone-mediated autophagy, and this leads to downstream consequences for macroautophagy. Thus, the similar (although not identical) ATG7 mutant mice, which both of our labs have developed, may mostly be modeling later stages in the disease.

    References:

    . PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010 Jan;8(1):e1000298. PubMed.

    . Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009 May 15;284(20) Epub 2009 Mar 10 PubMed.

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