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Autophagic pathways in Parkinson disease and related disorders

Published online by Cambridge University Press:  21 March 2011

Maria Xilouri  and
Leonidas Stefanis
Maria Xilouri
Affiliation:
Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Leonidas Stefanis*
Affiliation:
Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece Second Department of Neurology, University of Athens Medical School, Athens, Greece
*
*Corresponding author: Leonidas Stefanis, Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens (BRFAA) 4, Soranou Efesiou Street, Athens 11527, Greece. E-mail: lstefanis@bioacademy.gr
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Abstract

Macroautophagy and chaperone-mediated autophagy (CMA) are the two main mammalian lysosomal proteolytic systems. In macroautophagy, double-membrane structures engulf organelles and other intracellular constituents through a highly regulated process that involves the formation of autophagic vacuoles and their fusion with lysosomes. In CMA, selected proteins are targeted through a nonvesicular pathway to a transport complex at the lysosomal membrane, through which they are threaded into the lysosomes and degraded. Autophagy is important in development, differentiation, cellular remodelling and survival during nutrient starvation. Increasing evidence suggests that autophagic dysregulation causes accumulation of abnormal proteins or damaged organelles, which is a characteristic of chronic neurodegenerative conditions, such as Parkinson disease (PD). Evidence from post-mortem material, transgenic mice, and animal and cellular models of PD suggests that both major autophagic pathways are malfunctioning. Numerous connections exist between proteins genetically linked to autosomal dominant PD, in particular α-synuclein and LRRK2, and autophagic pathways. However, proteins involved in recessive PD, such as PINK1 and Parkin (PINK2), function in the process of mitophagy, whereby damaged mitochondria are selectively engulfed by macroautophagy. This wealth of new data suggests that both autophagic pathways are potential targets for therapeutic intervention in PD and other related neurodegenerative conditions.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e8
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts Publications

Autophagy forum is a very informative forum that allows positing of questions (pertaining to autophagy) by researchers or posting of relevant open positions:

Jaeger, P.A. and Wyss-Coray, T. (2009) All-you-can-eat: autophagy in neurodegeneration and neuroprotection. Molecular Neurodegeneration 4, 16Google Scholar
Mizushima, N., Yoshimori, T. and Levine, B. (2010) Methods in mammalian autophagy research. Cell 140, 313-326Google Scholar
Yang, Z. and Klionsky, D.J. (2010) Eaten alive: a history of macroautophagy. Nature Cell Biology 12, 814-822CrossRefGoogle ScholarPubMed
Koga, H. and Cuervo, A.M. (2010) Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiology of Disease, doi: 10.1016/j.nbd.2010.07.006Google Scholar
http://www.landesbioscience.com/journals/autophagy/forumGoogle Scholar
Jaeger, P.A. and Wyss-Coray, T. (2009) All-you-can-eat: autophagy in neurodegeneration and neuroprotection. Molecular Neurodegeneration 4, 16Google Scholar
Mizushima, N., Yoshimori, T. and Levine, B. (2010) Methods in mammalian autophagy research. Cell 140, 313-326Google Scholar
Yang, Z. and Klionsky, D.J. (2010) Eaten alive: a history of macroautophagy. Nature Cell Biology 12, 814-822CrossRefGoogle ScholarPubMed
Koga, H. and Cuervo, A.M. (2010) Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiology of Disease, doi: 10.1016/j.nbd.2010.07.006Google Scholar
http://www.landesbioscience.com/journals/autophagy/forumGoogle Scholar