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多发性硬化症的新型动物模型:髓鞘病理生理学中的R-Ras GTP酶

Novel Animal Models for Multiple Sclerosis: R-Ras GTPases in Myelin Pathophysiology.

作者信息

Esteban-Ortega Gema M, Garcia-Martin Gonzalo, Cubelos Beatriz

机构信息

Centro de Biología Molecular Severo Ochoa (CBM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.

Instituto Universitario de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

出版信息

Biomolecules. 2025 Sep 11;15(9):1309. doi: 10.3390/biom15091309.

Abstract

Demyelinating diseases, such as multiple sclerosis, involve oligodendrocyte death, myelin loss, and neuronal death. These processes have been extensively studied, and a causal relationship has been demonstrated between them: destruction of oligodendrocytes results in myelin deficiency, which subsequently leads to neurodegeneration and the consequent loss of sensory, motor, and cognitive functions. Currently, myelinopathies lack fully effective treatments. Available drugs primarily focus on controlling the immune response without directly promoting myelin regeneration or restoring neuronal functionality. Alongside these treatments, pharmaceutical research has increasingly focused on developing therapies that stimulate oligodendroglial lineage differentiation and myelin sheath regeneration. Despite these advances, the lack of suitable preclinical models has been a significant obstacle in evaluating new therapeutic compounds. In this review, we present the main animal models used in the preclinical phase for the study of myelin-related diseases and their role in the development of new therapies. In addition, we highlight the usefulness of R-Ras animal models for assessing the efficacy of compounds that promote oligodendrocyte differentiation.

摘要

脱髓鞘疾病,如多发性硬化症,涉及少突胶质细胞死亡、髓鞘丢失和神经元死亡。这些过程已得到广泛研究,并且已证明它们之间存在因果关系:少突胶质细胞的破坏导致髓鞘缺乏,随后导致神经退行性变以及随之而来的感觉、运动和认知功能丧失。目前,髓鞘病缺乏完全有效的治疗方法。现有的药物主要侧重于控制免疫反应,而没有直接促进髓鞘再生或恢复神经元功能。除了这些治疗方法外,药物研究越来越侧重于开发刺激少突胶质细胞谱系分化和髓鞘再生的疗法。尽管取得了这些进展,但缺乏合适的临床前模型一直是评估新治疗化合物的重大障碍。在这篇综述中,我们介绍了临床前阶段用于研究髓鞘相关疾病的主要动物模型及其在新疗法开发中的作用。此外,我们强调了R-Ras动物模型在评估促进少突胶质细胞分化的化合物疗效方面的有用性。

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