Astrocytes in heavy metal neurotoxicity and neurodegeneration.

Astrocytes in heavy metal neurotoxicity and neurodegeneration.
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星形胶质细胞在重金属神经毒性和神经变性中的作用

DOI:
10.1016/j.brainres.2020.147234
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发表时间:
2021-02-01
期刊:
影响因子:
2.9
通讯作者:
Verkhratsky A
Verkhratsky A
中科院分区:
医学3区
文献类型:
--
作者:
Li B;Xia M;Zorec R;Parpura V;Verkhratsky A

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随着工业的发展和环境污染的逐步加剧,人类对重金属的过度摄入成为一个紧迫的公共健康问题。过量摄入重金属,如砷(As)、锰(Mn)、汞(Hg)、铝(Al)、铅(Pb)、镍(Ni)、铋(Bi)、镉(Cd)、铜(Cu)、锌(Zn)和铁(Fe),具有神经毒性,会促进神经退化。星形胶质细胞是中枢神经系统中的主要稳态细胞。它们保护神经元免受各种类型的伤害,特别是通过积累重金属。然而,这使得星形胶质细胞成为重金属神经毒性的主要目标。重金属的摄入影响星形胶质细胞的稳态和神经保护级联反应,包括谷氨酸/GABA-谷氨酰胺穿梭,抗氧化机制和能量代谢。这些星形胶质细胞通路的缺陷促进甚至煽动神经变性。在这篇综述中,我们提供了一个简明的展望重金属诱导的星形胶质细胞病变及其与主要的神经退行性疾病。特别是,我们专注于铁诱导的神经毒性的星形胶质细胞机制。铁沉积在主要的神经退行性疾病中被检测到,如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。铁在脑中的蓄积与运动和认知障碍相关,铁诱导的组织病理学表现可被认为是神经退行性疾病的潜在诊断生物标志物。重金属神经毒性的有效管理可被视为预防或延缓神经退行性病变的潜在策略。
With the industrial development and progressive increase in environmental pollution, the mankind overexposure to heavy metals emerges as a pressing public health issue. Excessive intake of heavy metals, such as arsenic (As), manganese (Mn), mercury (Hg), aluminium (Al), lead (Pb), nickel (Ni), bismuth (Bi), cadmium (Cd), copper (Cu), zinc (Zn), and iron (Fe), is neurotoxic and it promotes neurodegeneration. Astrocytes are primary homeostatic cells in the central nervous system. They protect neurons against all types of insults, in particular by accumulating heavy metals. However, this makes astrocytes the main target for heavy metals neurotoxicity. Intake of heavy metals affects astroglial homeostatic and neuroprotective cascades including glutamate/GABA-glutamine shuttle, antioxidative machinery and energy metabolism. Deficits in these astroglial pathways facilitate or even instigate neurodegeneration. In this review, we provide a concise outlook on heavy metal-induced astroglio-pathies and their association with major neurodegenerative disorders. In particular, we focus on astroglial mechanisms of iron-induced neurotoxicity. Iron deposits in the brain are detected in main neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Accumulation of iron in the brain is associated with motor and cognitive impairments and iron-induced histopathological manifestations may be considered as the potential diagnostic biomarker of neurodegenerative diseases. Effective management of heavy metal neurotoxicity can be regarded as a potential strategy to prevent or retard neurodegenerative pathologies.
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