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. 2012:2012:429524.
doi: 10.1155/2012/429524. Epub 2012 Oct 17.

Parkinson's disease and autophagy

Ana María Sánchez-Pérez  1 , Berta Claramonte-Clausell, Juan Vicente Sánchez-Andrés, María Trinidad Herrero
Affiliations

Parkinson's disease and autophagy

Ana María Sánchez-Pérez et al. Parkinsons Dis. 2012.

Abstract

It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy.

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Figures

Figure 1
Figure 1
Schematic depiction of the three types of autophagy. (a) Chaperone-mediated autophagy. The cytosolic chaperone protein HSC 70 binds to the substrate protein; the consensus sequence LysPheGluArgGln of the substrate-chaperone complex is recognized by LAMP-2A, a lysosomal membrane receptor. The protein substrate is then unfolded and translocated across the lysosomal membrane to be degraded inside the lysosome. (b) Macroautophagy. Cytosolic material is sequestered by an expanding membrane sac (phagophore) forming a double-membrane vesicle, an autophagosome. Fusion of the autophagosome to the lysosome will expose the content of the autophagosome to lysosomal hydrolases. (c) Microautophagy. Small proteins can be engulfed directly by the lysosome without intermediate vesicles.
Figure 2
Figure 2
ROS/RNS production as a result of defective mitochondria respiratory activity can be induced by a number of factors like protein aggregates. Reactive species can also be generated by other cellular oxidases. These ROS/RNS species can modify several proteins which can stimulate and/or inhibit autophagy. In addition, reactive species produced or not in the mitochondria can target this organelle and induce further damage to it.
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