Roles of C/EBPβ/AEP in Neurodegenerative Diseases.

IF 2.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Current topics in medicinal chemistry Pub Date : 2025-01-27 DOI:10.2174/0115680266357822250119172351

Jing Guo, Xin-Yi Liu, Sha-Sha Yang, Qiang Li, Yang Duan, Shan-Shan Zhu, Ke Zhou, Yi-Zhi Yan, Peng Zeng

{"title":"Roles of C/EBPβ/AEP in Neurodegenerative Diseases.","authors":"Jing Guo, Xin-Yi Liu, Sha-Sha Yang, Qiang Li, Yang Duan, Shan-Shan Zhu, Ke Zhou, Yi-Zhi Yan, Peng Zeng","doi":"10.2174/0115680266357822250119172351","DOIUrl":null,"url":null,"abstract":"<p><p>In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266357822250119172351","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.

查看原文本刊更多论文

C/EBPβ/AEP在神经退行性疾病中的作用

近年来，越来越多的研究表明，天冬氨酸内肽酶（AEPs）激活增加是神经退行性疾病（ndd）的常见症状。AEP可裂解淀粉样蛋白前体蛋白（APP）、tau（微管相关蛋白tau）、α-突触核蛋白（α-syn）、SET（一种广泛表达于多种组织并主要定位于细胞核的39-KDa磷酸化蛋白）和TAR dna结合蛋白43 (TDP-43)，并促进其聚集，参与阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病、多发性硬化症（MS）、肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的发病机制。大量证据支持CCAAT/增强子结合蛋白β (C/EBPβ)/AEP可能在ndd中发挥重要作用的观点。开发其小分子抑制剂是一种很有前途的治疗ndd的方法。然而，目前的研究表明，ndd中C/EBPβ/AEP通路的病理生理机制非常复杂。本文就C/EBPβ和AEP的结构、主要生理功能、潜在发病机制、小分子抑制剂以及C/EBPβ/AEP如何为ndd的治疗提供新途径进行综述。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current topics in medicinal chemistry 医学-医药化学

CiteScore

6.40

自引率

2.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.