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多发性硬化症综述:揭示发病机制、疾病进展、相关机制及治疗创新的复杂性

A review on multiple sclerosis: Unravelling the complexities of pathogenesis, progression, mechanisms and therapeutic innovations.

作者信息

Rida Zainab Syeda, Zeb Khan Jehan, Khalid Tipu Muhammad, Jahan Faryal, Irshad Nadeem

机构信息

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Shifa College of Pharmaceutical Sciences, STMU, Islamabad, Pakistan.

出版信息

Neuroscience. 2025 Feb 16;567:133-149. doi: 10.1016/j.neuroscience.2024.12.029. Epub 2024 Dec 19.

Abstract

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.e. autoreactive T & B-Cells and macrophage infiltration into the CNS leads to inflammation, demyelination, and neurodegeneration. Disease progression of MS varies among individuals transitioning from one form of relapsing-remitting to secondary progressive MS (SPMS). Research advances have unfolded various molecular targets involved in MS from oxidative stress to blood-brain barrier (BBB) disruption. Different pathways are being targeted so far such as inflammatory and cytokine signaling pathways to overcome disease progression. Therapeutic innovations have significantly transformed the management of MS, especially the use of disease-modifying therapies (DMTs) to reduce relapse rates and control disease progression. Advancements in research, neuroprotective strategies, and remyelination strategies hold promising results in reversing CNS damage. Various mice models are being adopted for testing new entities in MS research.

摘要

多发性硬化症(MS)是一种针对有髓轴突的中枢神经系统(CNS)慢性炎症性脱髓鞘疾病。MS的发病机制涉及复杂的遗传、环境和免疫相互作用。免疫反应失调,即自身反应性T细胞和B细胞以及巨噬细胞浸润到中枢神经系统会导致炎症、脱髓鞘和神经变性。MS的疾病进展在个体之间有所不同,可从复发缓解型转变为继发进展型MS(SPMS)。研究进展揭示了MS中涉及的各种分子靶点,从氧化应激到血脑屏障(BBB)破坏。目前正在针对不同的途径,如炎症和细胞因子信号通路,以克服疾病进展。治疗创新显著改变了MS的管理,特别是使用疾病修饰疗法(DMTs)来降低复发率和控制疾病进展。研究、神经保护策略和髓鞘再生策略的进展在逆转中枢神经系统损伤方面取得了有希望的结果。在MS研究中正在采用各种小鼠模型来测试新的药物。

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