title: Role of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation.
abstract: 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 (α-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 α-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 α-Syn aggregation and neurodegeneration. We will also discuss other factors such as traumatic brain injury and oxidative insult in the context of α-Syn-related neurodegenerative processes.
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Dharmin
authors.initials: D
authors.lastname: Rokad
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Shivani
authors.initials: S
authors.lastname: Ghaisas
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Dilshan S
authors.initials: DS
authors.lastname: Harischandra
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Huajun
authors.initials: H
authors.lastname: Jin
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Vellareddy
authors.initials: V
authors.lastname: Anantharam
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
authors.forename: Arthi
authors.initials: A
authors.lastname: Kanthasamy
authors.affiliation: Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States. Electronic address: akanthas@iastate.edu.
authors.forename: Anumantha G
authors.initials: AG
authors.lastname: Kanthasamy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism; D010575:Pesticides / Q000009:adverse effects; D066329:Protein Aggregates / Q000502:physiology*; D057165:Proteostasis Deficiencies / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: D010575:Pesticides; D066329:Protein Aggregates; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Metals; Neurodegenerative disease; Oxidative stress; Parkinson disease; Pesticides; Protein aggregation; Traumatic brain injury