Synaptic scaffold protein PSD-95: a therapeutic target for Alzheimer's disease.

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-10-03 DOI:10.1016/j.bcp.2025.117401

Xing Fan, Hao Wang, Jianchao Ping, Mingzhe Li, Jianlan Gu, Wei Qian

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引用次数: 0

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder marked by gradual cognitive deterioration and distinct neuropathological characteristics. The abnormal accumulation of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) are the hallmarks of AD. In fact, synaptic loss and damage occur earlier than amyloid plaques and NFTs in the progression of AD and are most closely associated with the cognitive deficits exhibited by AD patients. In this review, we discuss the expression level, localization, posttranslational modification and interaction proteins of PSD-95, as well as their roles in synaptic plastisity. We also review the mechanisms through which PSD-95 contributes to synaptic dysfunction in AD. Moreover, the potential of PSD-95 as an early biomarker for AD is also discussed, along with the therapeutic approaches that target PSD-95 for patients afflicted with the disease. The objective of this review is to offer comprehensive insights into the early pathogenesis of Alzheimer's disease and to aid in the development of novel diagnostic and treatment methodologies grounded in this understanding.

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突触支架蛋白PSD-95：阿尔茨海默病的治疗靶点

阿尔茨海默病（Alzheimer's disease， AD）是一种慢性神经退行性疾病，其特点是认知能力逐渐退化，神经病理特征明显。淀粉样蛋白-β (Aβ)和神经原纤维缠结（nft）的异常积累是阿尔茨海默病的标志。事实上，在阿尔茨海默病的发展过程中，突触丧失和损伤比淀粉样斑块和nft发生得更早，并且与阿尔茨海默病患者表现出的认知缺陷最密切相关。本文就PSD-95的表达水平、定位、翻译后修饰和相互作用蛋白及其在突触可塑性中的作用进行综述。我们也回顾了PSD-95在AD患者突触功能障碍中的作用机制。此外，本文还讨论了PSD-95作为AD早期生物标志物的潜力，以及针对该疾病患者的PSD-95治疗方法。本综述的目的是为阿尔茨海默病的早期发病机制提供全面的见解，并有助于在此基础上开发新的诊断和治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.