作为神经退行性疾病潜在靶点的 VPS35 或 retromer:前进的障碍。

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-22 DOI:10.1080/14728222.2024.2392700
Anika Wu, Daehoon Lee, Wen-Cheng Xiong
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引用次数: 0

摘要

导言:空泡蛋白分拣 35(VPS35)在 retromer 复合物中起着关键作用,负责细胞内跨膜蛋白的运输,其功能障碍与神经退行性疾病有关。一种错义突变 Asp620Asn (D620N) 与家族性晚期帕金森氏症密切相关,而在阿尔茨海默氏症、肌萎缩性脊髓侧索硬化症(ALS)、额颞叶痴呆症(FTD)和陶氏病中都能观察到 VPS35 水平的降低。某些神经元在发育过程中缺失 VPS35 会导致神经退行性变,因此 VPS35 对神经健康至关重要。目前的治疗研究主要针对清除有害蛋白聚集体和控制症状。以 VPS35 为重点的创新疗法正在研究之中,但充分了解其机制和最佳靶向策略仍是一项挑战:本综述详细介绍了 VPS35 的发现、其在神经退行性机制中的作用--尤其是在帕金森氏症和阿尔茨海默氏症中的作用--及其与其他疾病的联系。专家观点:VPS35 是细胞功能不可或缺的一部分:VPS35与细胞功能和疾病相关,是开发疗法的重要候选对象。调节 VPS35 活性的研究进展可能会带来突破性的治疗方法,不仅能延缓疾病进展,还能作为神经变性风险的生物标志物,从而在控制这些复杂疾病方面向前迈出一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.

Introduction: Vacuolar Protein Sorting 35 (VPS35) is pivotal in the retromer complex, governing transmembrane protein trafficking within cells, and its dysfunction is implicated in neurodegenerative diseases. A missense mutation, Asp620Asn (D620N), specifically ties to familial late-onset Parkinson's, while reduced VPS35 levels are observed in Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and tauopathies. VPS35's absence in certain neurons during development can initiate neurodegeneration, highlighting its necessity for neural health. Present therapeutic research mainly targets the clearance of harmful protein aggregates and symptom management. Innovative treatments focusing on VPS35 are under investigation, although fully understanding the mechanisms and optimal targeting strategies remain a challenge.

Areas covered: This review offers a detailed account of VPS35's discovery, its role in neurodegenerative mechanisms - especially in Parkinson's and Alzheimer's - and its link to other disorders. It shines alight on recent insights into VPS35's function in development, disease, and as a therapeutic target.

Expert opinion: VPS35 is integral to cellular function and disease association, making it a significant candidate for developing therapies. Progress in modulating VPS35's activity may lead to breakthrough treatments that not only slow disease progression but may also act as biomarkers for neurodegeneration risk, marking a step forward in managing these complex conditions.

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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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