Agrochemicals-Induced Dopaminergic Neurotoxicity: Role of Mitochondria-Mediated Oxidative Stress and Protein Clearance Mechanisms

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder that is characterized by the progressive loss of substantia nigral dopaminergic neurons resulting in the pronounced depletion of striatal DA levels which subsequently leads to the expression of cardinal features of PD including tremor, bradykinesia, rigidity and postural instability. The mechanisms underlying the selective loss of dopaminergic neurons remain poorly understood; however, studies conducted in post mortem PD brains and experimental PD models have implicated oxidative stress and mitochondrial dysfunction in the mechanism of dopaminergic neurodegeneration. In recent years, the etiology of several neurodegenerative diseases including PD has been linked to low dose and chronic exposure to a variety of agrochemicals including paraquat, rotenone and dieldrin. Here we discuss how several of these pesticides share common mechanistic events, including oxidative stress, mitochondrial impairment/complex I inhibition, abnormal protein aggregation and post translational modifications (PTMs) of proteins including α-synuclein, as well as dopaminergic cell death. Furthermore, intersecting and parallel effects of environmental neurotoxicants on protein clearance mechanisms and mitochondrial function are addressed and hence provide novel insights that might be beneficial in the development of targeted therapies for PD.

Department(s)

Biological Sciences

Comments

Chapter 10

This study was supported by grants from the National Institute of Health NS65167 and NS78247 and ES10586.

Keywords and Phrases

Autophagy; Mitochondrial dysfunction; Neurodegeneration; Oxidative stress; Parkinson’s disease; Pesticides; UPS

International Standard Book Number (ISBN)

978-3-319-13938-8; 978-3-319-13939-5

Document Type

Book - Chapter

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2015 Springer International Publishing, All rights reserved.

Publication Date

01 Jan 2015

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