Rokad Dharmin, Ghaisas Shivani, Harischandra Dilshan S, Jin Huajun, Anantharam Vellareddy, Kanthasamy Arthi, Kanthasamy Anumantha G
Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
Brain Res Bull. 2017 Jul;133:60-70. doi: 10.1016/j.brainresbull.2016.12.003. Epub 2016 Dec 16.
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.
蛋白质错误折叠和聚集是包括帕金森病（PD）和其他形式人类帕金森综合征在内的许多神经退行性疾病的关键病理特征。PD是一种复杂且多方面的疾病，其病因尚未完全明确。然而，多条证据支持多重打击假说，即遗传易感性和环境毒物共同作用引发PD病理。大脑中α-突触核蛋白（α-Syn）聚集是包括PD在内的突触核蛋白病的重要病理生理特征。流行病学和实验研究表明，金属和农药在α-Syn聚集导致包括PD在内的各种神经退行性疾病发病过程中起关键作用。在这篇综述中，我们将重点介绍几项关于金属和农药诱导α-Syn聚集及神经变性的流行病学和实验研究的主要发现。我们还将在α-Syn相关神经退行性过程的背景下讨论其他因素，如创伤性脑损伤和氧化损伤。
