Toxin-induced models of Parkinson's disease

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease that appears essentially as a sporadic condition. It results mainly from the death of dopaminergic neurons in the substantia nigra. PD etiology remains mysterious, whereas its pathogenesis begins to be understood as a multifactorial cascade of deleterious factors. Most insights into PD pathogenesis come from investigations performed in experimental models of PD, especially those produced by neurotoxins. Although a host of natural and synthetic molecules do exert deleterious effects on dopaminergic neurons, only a handful are used in living laboratory animals to recapitulate some of the hallmarks of PD. In this review, we discuss what we believe are the four most popular parkinsonian neurotoxins, namely 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat. The main goal is to provide an updated summary of the main characteristics of each of these four neurotoxins. However, we also try to provide the reader with an idea about the various strengths and the weaknesses of these neurotoxic models.

FIG. 1.

Oxidation of 6-OHDA. Used with permission from Przedborski and Ischiropoulos. Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson’s disease. Antioxid Redox Signal 7:685–693. Copyright © 2005, Mary Ann Liebert, Inc. All rights reserved.

FIG. 2.

Comparison of chemical structures of MPPP and MPTP.

FIG. 3.

Chemical structure of rotenone.

FIG. 4.

Reduction-oxidation cycling reaction of paraquat.

FIG. 5.

Comparison of chemical structures of MPP⁺ and paraquat. Used with permission from Przedborski and Ischiropoulos. Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson’s disease. Antioxid Redox Signal 7:685–693. Copyright © 2005, Mary Ann Liebert, Inc. All rights reserved.