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揭示 STEP61 在阿尔茨海默病中的意义:结构、底物和相互作用组。

Uncovering the Significance of STEP61 in Alzheimer's Disease: Structure, Substrates, and Interactome.

机构信息

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.

Clinical Research Unit (CRU Global Hungary Ltd.), Budapest, Hungary.

出版信息

Cell Mol Neurobiol. 2023 Oct;43(7):3099-3113. doi: 10.1007/s10571-023-01364-2. Epub 2023 May 23.

Abstract

STEP (STriatal-Enriched Protein Tyrosine Phosphatase) is a brain-specific phosphatase that plays an important role in controlling signaling molecules involved in neuronal activity and synaptic development. The striatum is the main location of the STEP enzyme. An imbalance in STEP61 activity is a risk factor for Alzheimer's disease (AD). It can contribute to the development of numerous neuropsychiatric diseases, including Parkinson's disease (PD), schizophrenia, fragile X syndrome (FXS), Huntington's disease (HD), alcoholism, cerebral ischemia, and stress-related diseases. The molecular structure, chemistry, and molecular mechanisms associated with STEP61's two major substrates, Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAr) and N-methyl-D-aspartate receptors (NMDARs), are crucial in understanding the relationship between STEP61 and associated illnesses. STEP's interactions with its substrate proteins can alter the pathways of long-term potentiation and long-term depression. Therefore, understanding the role of STEP61 in neurological illnesses, particularly Alzheimer's disease-associated dementia, can provide valuable insights for possible therapeutic interventions. This review provides valuable insights into the molecular structure, chemistry, and molecular mechanisms associated with STEP61. This brain-specific phosphatase controls signaling molecules involved in neuronal activity and synaptic development. This review can aid researchers in gaining deep insights into the complex functions of STEP61.

摘要

STEP(纹状体丰富的蛋白酪氨酸磷酸酶)是一种脑特异性磷酸酶,在控制神经元活动和突触发育涉及的信号分子方面发挥着重要作用。纹状体是 STEP 酶的主要位置。STEP61 活性失衡是阿尔茨海默病(AD)的一个风险因素。它可能导致许多神经精神疾病的发展,包括帕金森病(PD)、精神分裂症、脆性 X 综合征(FXS)、亨廷顿病(HD)、酒精中毒、脑缺血和应激相关疾病。了解 STEP61 与其相关疾病之间的关系,关键在于了解其两个主要底物 Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPAr)和 N-methyl-D-aspartate receptors(NMDARs)的分子结构、化学和分子机制。STEP 与其底物蛋白的相互作用可以改变长时程增强和长时程抑制的途径。因此,了解 STEP61 在神经疾病中的作用,特别是与阿尔茨海默病相关的痴呆症,可以为可能的治疗干预提供有价值的见解。本综述提供了对 STEP61 相关的分子结构、化学和分子机制的有价值的见解。这种脑特异性磷酸酶控制涉及神经元活动和突触发育的信号分子。本综述可以帮助研究人员深入了解 STEP61 的复杂功能。

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