脑海绵状畸形的激酶:发病机制和治疗靶点

IF 4.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chunxiao Qi , Richard Sean Bujaroski , Jonathan Baell , Xiangjian Zheng
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引用次数: 0

摘要

脑海绵状畸形(CCMs)是一种低流量、出血性的中枢神经系统血管病变,可引起中风样症状和癫痫发作。从CCM1、CCM2和CCM3作为与疾病进展相关的基因的鉴定,已经建立了CCM发病机制的分子和细胞机制,并开始寻找靶向CCM的潜在药物。从广义上讲,激酶是CCM发病机制中的主要信号传导群。这些包括MEKK3/MEK5/ERK5级联、Rho/Rock信号传导、CCM3/GCKIII信号传导、PI3K/mTOR信号传导等。自从在CCM发病机制中发现Rho/Rock以来,Rho信号传导抑制剂以及随后CCM信号传导中的其他成分被发现并应用于临床前和临床试验,以改善CCM的进展。这篇综述讨论了CCM疾病的一般方面,CCM发病机制中激酶介导的信号传导,以及CCM潜在治疗方案的现状。有人认为,CCM背景下的激酶靶向药物开发可能促进并满足未满足的需求——CCM疾病的非手术选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kinases in cerebral cavernous malformations: Pathogenesis and therapeutic targets

Cerebral cavernous malformations (CCMs) are low-flow, hemorrhagic vascular lesions of the central nervous system of genetic origin, which can cause stroke-like symptoms and seizures. From the identification of CCM1, CCM2 and CCM3 as genes related to disease progression, molecular and cellular mechanisms for CCM pathogenesis have been established and the search for potential drugs to target CCM has begun. Broadly speaking, kinases are the major group signaling in CCM pathogenesis. These include the MEKK3/MEK5/ERK5 cascade, Rho/Rock signaling, CCM3/GCKIII signaling, PI3K/mTOR signaling, and others. Since the discovery of Rho/Rock in CCM pathogenesis, inhibitors for Rho signaling and subsequently other components in CCM signaling were discovered and applied in preclinical and clinical trials to ameliorate CCM progression. This review discusses the general aspects of CCM disease, kinase-mediated signaling in CCM pathogenesis and the current state of potential treatment options for CCM. It is suggested that kinase target drug development in the context of CCM might facilitate and meet the unmet requirement – a non-surgical option for CCM disease.

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来源期刊
CiteScore
10.00
自引率
2.00%
发文量
151
审稿时长
44 days
期刊介绍: BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.
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