Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders.

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders.
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DOI:
10.3389/fncir.2021.711564
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发表时间:
2021
影响因子:
3.5
通讯作者:
Ma YY
Ma YY
中科院分区:
医学3区
文献类型:
--
作者:
Guo C;Ma YY

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兴奋性毒性是中枢和外周神经系统多种疾病中细胞损失的主要机制之一。除了先前建立的兴奋性毒性的信号传导途径(其依赖于从轴突末端过度释放谷氨酸或过度激活NMDA受体(NMDAR))之外,在多种疾病模型中检测到通过Ca 2+渗透性(CP)-AMPA受体(AMPAR)的Ca 2+内流触发的兴奋性毒性。在这篇综述中,急性脑损伤(例如,脑外伤或脊髓损伤、局部缺血)和慢性神经系统疾病,包括癫痫/癫痫发作、亨廷顿氏病(HD)、帕金森氏病(PD)、阿尔茨海默氏病(AD)、肌萎缩性侧索硬化(ALS)、慢性疼痛和青光眼,讨论了CP-AMPAR介导的兴奋性毒性。考虑到大多数细胞中CP-AMPAR的低表达或缺乏,特异性操纵CP-AMPAR可能是一种更合理的策略,以延迟病理学改变的发生和进展,副作用比阻断NMDAR更少。
Excitotoxicity is one of the primary mechanisms of cell loss in a variety of diseases of the central and peripheral nervous systems. Other than the previously established signaling pathways of excitotoxicity, which depend on the excessive release of glutamate from axon terminals or over-activation of NMDA receptors (NMDARs), Ca2+ influx-triggered excitotoxicity through Ca2+-permeable (CP)-AMPA receptors (AMPARs) is detected in multiple disease models. In this review, both acute brain insults (e.g., brain trauma or spinal cord injury, ischemia) and chronic neurological disorders, including Epilepsy/Seizures, Huntington’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), chronic pain, and glaucoma, are discussed regarding the CP-AMPAR-mediated excitotoxicity. Considering the low expression or absence of CP-AMPARs in most cells, specific manipulation of the CP-AMPARs might be a more plausible strategy to delay the onset and progression of pathological alterations with fewer side effects than blocking NMDARs.
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