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Review
. 2012 Dec;46(3):639-61.
doi: 10.1007/s12035-012-8318-1. Epub 2012 Aug 17.

Defective autophagy in Parkinson's disease: role of oxidative stress

Elzbieta Janda  1 , Ciro Isidoro, Cristina Carresi, Vincenzo Mollace
Affiliations
Review

Defective autophagy in Parkinson's disease: role of oxidative stress

Elzbieta Janda et al. Mol Neurobiol. 2012 Dec.

Abstract

Parkinson's disease (PD) is a paradigmatic example of neurodegenerative disorder with a critical role of oxidative stress in its etiopathogenesis. Genetic susceptibility factors of PD, such as mutations in Parkin, PTEN-induced kinase 1, and DJ-1 as well as the exposure to pesticides and heavy metals, both contribute to altered redox balance and degeneration of dopaminergic neurons in the substantia nigra. Dysregulation of autophagy, a lysosomal-driven process of self degradation of cellular organelles and protein aggregates, is also implicated in PD and PD-related mutations, and environmental toxins deregulate autophagy. However, experimental evidence suggests a complex and ambiguous role of autophagy in PD since either impaired or abnormally upregulated autophagic flux has been shown to cause neuronal loss. Finally, it is generally believed that oxidative stress is a strong proautophagic stimulus. However, some evidence coming from neurobiology as well as from other fields indicate an inhibitory role of reactive oxygen species and reactive nitrogen species on the autophagic machinery. This review examines the scientific evidence supporting different concepts on how autophagy is dysregulated in PD and attempts to reconcile apparently contradictory views on the role of oxidative stress in autophagy regulation. The complex relationship between autophagy and oxidative stress is also considered in the context of the ongoing search for a novel PD therapy.

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References

    1. Science. 2004 Aug 27;305(5688):1292-5 - PubMed
    1. Neurochem Int. 2010 Oct;57(3):198-205 - PubMed
    1. Nature. 1998 Oct 1;395(6701):451-2 - PubMed
    1. Mol Neurobiol. 2012 Feb;45(1):126-43 - PubMed
    1. Annu Rev Genet. 2009;43:67-93 - PubMed

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