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How Parkinsonian Toxins Dysregulate the Autophagy Machinery
Department of Pharmacology, University of Nevada School of Medicine, Manville Building 18A, Reno, NV 89557, USA
Department of Health Sciences, Magna Graecia University, Campus Germaneto, 88100 Cantazaro, Italy
* Author to whom correspondence should be addressed.
Received: 30 September 2013; in revised form: 28 October 2013 / Accepted: 28 October 2013 / Published: 8 November 2013
Abstract: Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone) have been widely employed as in vivo and in vitro chemical models of Parkinson’s disease (PD). Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD.
Keywords: MPTP; 6-hydroxydopamine; rotenone; paraquat; methamphetamine; autophagy; mitophagy; Parkinson’s disease
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Dagda, R.K.; Banerjee, T.D.; Janda, E. How Parkinsonian Toxins Dysregulate the Autophagy Machinery. Int. J. Mol. Sci. 2013, 14, 22163-22189.
Dagda RK, Banerjee TD, Janda E. How Parkinsonian Toxins Dysregulate the Autophagy Machinery. International Journal of Molecular Sciences. 2013; 14(11):22163-22189.
Dagda, Ruben K.; Banerjee, Tania D.; Janda, Elzbieta. 2013. "How Parkinsonian Toxins Dysregulate the Autophagy Machinery." Int. J. Mol. Sci. 14, no. 11: 22163-22189.