Abstract:
Neuroinflammation and mitochondrial dysfunction are closely intertwined with the pathophysiology of neurological disorders. Recent studies have elucidated profound alterations in mitochondrial dynamics across a spectrum of neurological disorders. Dynamin-related protein 1 (DRP1) emerges as a pivotal regulator of mitochondrial fission, with its dysregulation disrupting mitochondrial homeostasis and fueling neuroinflammation, thereby exacerbating disease severity. In addition to its role in mitochondrial dynamics, DRP1 plays a crucial role in modulating inflammation-related pathways. This review synthesizes important functions of DRP1 in the central nervous system (CNS) and the impact of epigenetic modification on the progression of neurodegenerative diseases. The intricate interplay between neuroinflammation and DRP1 in microglia and astrocytes, central contributors to neuroinflammation, is expounded upon. Furthermore, the use of DRP1 inhibitors to influence the activation of microglia and astrocytes, as well as their involvement in processes such as mitophagy, mitochondrial oxidative stress, and calcium ion transport in CNS-mediated neuroinflammation, is scrutinized. The modulation of microglia to astrocyte crosstalk by DRP1 and its role in inflammatory neurodegeneration is also highlighted. Overall, targeting DRP1 presents a promising avenue for ameliorating neuroinflammation and enhancing the therapeutic management of neurological disorders.
摘要:
神经炎症和线粒体功能障碍与神经系统疾病的病理生理密切相关。最近的研究已经阐明了一系列神经系统疾病中线粒体动力学的深刻变化。动态蛋白相关蛋白1(DRP1)是线粒体裂变的关键调节因子,它的失调破坏了线粒体稳态并加剧了神经炎症,从而加剧疾病的严重程度。除了它在线粒体动力学中的作用,DRP1在调节炎症相关途径中起着至关重要的作用。本文综述了DRP1在中枢神经系统(CNS)中的重要功能以及表观遗传修饰对神经退行性疾病进展的影响。小胶质细胞和星形胶质细胞中神经炎症和DRP1之间的复杂相互作用,神经炎症的主要贡献者,被阐述了。此外,使用DRP1抑制剂影响小胶质细胞和星形胶质细胞的活化,以及它们参与线粒体自噬等过程,线粒体氧化应激,和钙离子转运在中枢神经系统介导的神经炎症,正在仔细检查。还强调了DRP1对小胶质细胞对星形胶质细胞串扰的调节及其在炎性神经变性中的作用。总的来说,靶向DRP1为改善神经炎症和增强神经系统疾病的治疗管理提供了有希望的途径.