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KMID : 0043320210440070668
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Archives of Pharmacal Research
2021 Volume.44 No. 7 p.668 ~ p.688
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Methamphetamine-induced dopaminergic neurotoxicity as a model of Parkinson’s disease
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Shin Eun-Joo
Jeong Ji-Hoon
Hwang Yeong-Gwang
Sharma Naveen
Dang Duy-Khanh
Nguyen Bao-Trong
Nah Seung-Yeol
Jang Choon-Gon
Bing Guoying
Nabeshima Toshitaka
Kim Hyoung-Chun
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Abstract
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Parkinson’s disease (PD) is a progressive neurodegenerative disease with a high prevalence, approximately 1?% in the elderly population. Numerous studies have demonstrated that methamphetamine (MA) intoxication caused the neurological deficits and nigrostriatal damage seen in Parkinsonian conditions, and subsequent rodent studies have found that neurotoxic binge administration of MA reproduced PD-like features, in terms of its symptomatology and pathology. Several anti-Parkinsonian medications have been shown to attenuate the motor impairments and dopaminergic damage induced by MA. In addition, it has been recognized that mitochondrial dysfunction, oxidative stress, pro-apoptosis, proteasomal/autophagic impairment, and neuroinflammation play important roles in inducing MA neurotoxicity. Importantly, MA neurotoxicity has been shown to share a common mechanism of dopaminergic toxicity with that of PD pathogenesis. This review describes the major findings on the neuropathological features and underlying neurotoxic mechanisms induced by MA and compares them with Parkinsonian pathogenesis. Taken together, it is suggested that neurotoxic binge-type administration of MA in rodents is a valid animal model for PD that may provide knowledge on the neuropathogenesis of PD.
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KEYWORD
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Methamphetamine, Dopaminergic neurotoxicity, Parkinson’s disease, Animal model
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