NOTCH3在CADASIL发病机制中的作用：新疗法的见解

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-05-31 DOI:10.1016/j.brainres.2025.149754

Favour Felix-Ilemhenbhio , Klaudia Kocsy , Mimoun Azzouz , Arshad Majid

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引用次数: 0

摘要

脑常染色体显性动脉病伴皮层下梗死和白质脑病（CADASIL）是一种单基因遗传性小血管疾病，其特征是反复发作的皮层下缺血性中风、认知能力下降和其他神经系统症状。NOTCH3基因内的单核苷酸突变可损害NOTCH3加工和/或信号传导，导致颗粒性亲渗物质（GOM）在血管壁积累，从而导致CADASIL。尽管它具有显著的临床影响，但目前尚无针对CADASIL的明确治疗方法。本文对CADASIL的病理生理机制进行了全面分析，重点关注NOTCH3突变及其对蛋白质加工和信号传导的影响。这篇综述提出了一个假说来解释NOTCH3突变如何改变信号传导过程并导致GOMs。此外，该综述探讨了旨在恢复正常NOTCH3功能的已发表的治疗策略。

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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The role of NOTCH3 in CADASIL pathogenesis: insights into novel therapies

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenetic hereditary small-vessel disorder characterised by recurrent subcortical ischemic strokes, cognitive deterioration, and other neurological symptoms. Single nucleotide mutations within the NOTCH3 gene can impair NOTCH3 processing and/or signalling, resulting in the accumulation of granular osmiophilic material (GOM) in blood vessel walls, and consequently CADASIL. Despite its significant clinical impact, there is currently no definitive treatment for CADASIL. This review provides a comprehensive analysis of the pathophysiological mechanisms underlying CADASIL, focusing on NOTCH3 mutations and their effects on protein processing and signalling. The review proposes a hypothesis that explains how NOTCH3 mutations may alter the signalling process and result in GOMs. Additionally, the review explores published therapy strategies aimed at restoring normal NOTCH3 function.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.