Journal
BRAIN RESEARCH BULLETIN
Volume 133, Issue -, Pages 60-70Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2016.12.003
Keywords
Alpha-synuclein; Pesticides; Metals; Protein aggregation; Traumatic brain injury; Oxidative stress; Parkinson disease; Neurodegenerative disease
Categories
Funding
- National Institutes of Health [ES19267, ES26892, NS074443, ES10586, N5088206]
- Linda Lloyd Endowed Chair
- Syngenta Fellowship Award in Human Health Applications of New Technologies
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Protein misfolding and aggregation are key pathological features of many neurodegenerative diseases including Parkinson's disease (PD) and other forms of human Parkinsonism. PD is a complex and multifaceted disorder whose etiology is not fully understood. However, several lines of evidence support the multiple hit hypothesis that genetic vulnerability and environmental toxicants converge to trigger PD pathology. Alpha-synuclein (alpha-Syn) aggregation in the brain is an important pathophysiological characteristic of synucleinopathies including PD. Epidemiological and experimental studies have shown that metals and pesticides play a crucial role in alpha-Syn aggregation leading to the onset of various neurodegenerative diseases including PD. In this review, we will emphasize key findings of several epidemiological as well as experimental studies of metal- and pesticide-induced alpha-Syn aggregation and neurodegeneration. We will also discuss other factors such as traumatic brain injury and oxidative insult in the context of alpha-Syn-related neurodegenerative processes. (C) 2016 Elsevier Inc. All rights reserved.
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