Mitochondrial complex I inhibitor rotenone-induced toxicity and its potential mechanisms in Parkinson's disease models

• Published in: Critical reviews in toxicology Vol. 42; no. 7; pp. 613 - 632
• Main Authors: Xiong, Nian, Long, Xi, Xiong, Jing, Jia, Min, Chen, Chunnuan, Huang, Jinsha, Ghoorah, Devina, Kong, Xiangquan, Lin, Zhicheng, Wang, Tao
• Format: Journal Article
• Language: English
• Published: London Informa Healthcare 01.08.2012; Taylor & Francis
• Subjects: alpha-Synuclein - metabolism; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; dopaminergic neuron; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - pathology; Humans; Lewy Bodies - drug effects; Lewy Bodies - pathology; mechanism; Medical sciences; Mitochondria - drug effects; Mitochondria - metabolism; Nervous system (semeiology, syndromes); Nervous system as a whole; neurodegeneration; Neurology; Oxidative Stress - drug effects; Parkinson Disease - etiology; Parkinson Disease - pathology; Parkinson's disease; pathogenesis; Proteolysis - drug effects; rotenone; Rotenone - toxicity; Substantia Nigra - drug effects; Substantia Nigra - pathology; Animal model; Nervous system diseases; Parkinson's disease; Rat; Pathogenesis; Toxicity; Rodentia; Parkinson disease; neurodegeneration; rotenone; Cerebral disorder; Vertebrata; Mitochondria; Mammalia; Mouse; Etiology; Central nervous system disease; Dopaminergic neuron; Degenerative disease; Inhibitor; Mechanism of action; mechanism; Extrapyramidal syndrome
• ISSN: 1040-8444; 1547-6898
• DOI: 10.3109/10408444.2012.680431

The etiology of Parkinson's disease (PD) is attributed to both environmental and genetic factors. The development of PD reportedly involves mitochondrial impairment, oxidative stress, α-synuclein aggregation, dysfunctional protein degradation, glutamate toxicity, calcium overloading, inflammation and loss of neurotrophic factors. Based on a link between mitochondrial dysfunction and pesticide exposure, many laboratories, including ours, have recently developed parkinsonian models by utilization of rotenone, a well-known mitochondrial complex I inhibitor. Rotenone models for PD appear to mimic most clinical features of idiopathic PD and recapitulate the slow and progressive loss of dopaminergic (DA) neurons and the Lewy body formation in the nigral-striatal system. Notably, potential human parkinsonian pathogenetic and pathophysiological mechanisms have been revealed through these models. In this review, we summarized various rotenone-based models for PD and discussed the implied etiology of and treatment for PD