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Defective Autophagy in Parkinson’s Disease: Role of Oxidative Stress

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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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Acknowledgments

E. Janda, V. Mollace, and C. Carresi acknowledge Environmental Protection Agency (ARPACal) for research funding. Research on autophagy and neurodegeneration in the laboratory of C. Isidoro were funded by Compagnia S. Paolo di Torino (Neuroscience Project 2009).

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Authors and Affiliations

  1. Department of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, viale Europa, Campus Salvatore Venuta, Germaneto, 88100, Catanzaro, Italy

    Elzbieta Janda, Cristina Carresi & Vincenzo Mollace

  2. Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Novara, Italy

    Ciro Isidoro

  3. San Raffaele Pisana, L’Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy

    Vincenzo Mollace

  4. Salus Research Institute, Marinella di Bruzzano (RC), Italy

    Vincenzo Mollace

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  1. Elzbieta Janda
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  2. Ciro Isidoro
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  3. Cristina Carresi
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  4. Vincenzo Mollace
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Correspondence to Elzbieta Janda.

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Janda, E., Isidoro, C., Carresi, C. et al. Defective Autophagy in Parkinson’s Disease: Role of Oxidative Stress. Mol Neurobiol 46, 639–661 (2012). https://doi.org/10.1007/s12035-012-8318-1

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  • DOI: https://doi.org/10.1007/s12035-012-8318-1

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