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

Abstract

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

Keywords::

• Parkinson’s disease
• rotenone
• pathogenesis
• dopaminergic neuron
• neurodegeneration
• mechanism

Acknowledgments

The authors would like to thank Dr. Shenggang Sun, Dr. Yuanwu Mei, and Dr. Changqin Liu (Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) for their valuable insights on the manuscript

Declaration of interest

This work was supported by grants 30870866, 81071021 and 31171211 from the National Natural Science Foundation of China (to TW) and grant 20066002100 from the Wuhan Science and Technology Bureau, China (to TW). The authors alone are responsible for the content and writing of the paper