Department of Physiology and Pathophysiology, Regenerative Medicine Program, Spinal Cord Research Centre, Children's Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Physiology and Pathophysiology, Regenerative Medicine Program, Spinal Cord Research Centre, Children's Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Biochim Biophys Acta Mol Basis Dis. 2021 Jun 1;1867(6):166117. doi: 10.1016/j.bbadis.2021.166117. Epub 2021 Mar 2.
White matter degeneration is an important pathophysiological event of the central nervous system that is collectively characterized by demyelination, oligodendrocyte loss, axonal degeneration and parenchymal changes that can result in sensory, motor, autonomic and cognitive impairments. White matter degeneration can occur due to a variety of causes including trauma, neurotoxic exposure, insufficient blood flow, neuroinflammation, and developmental and inherited neuropathies. Regardless of the etiology, the degeneration processes share similar pathologic features. In recent years, a plethora of cellular and molecular mechanisms have been identified for axon and oligodendrocyte degeneration including oxidative damage, calcium overload, neuroinflammatory events, activation of proteases, depletion of adenosine triphosphate and energy supply. Extensive efforts have been also made to develop neuroprotective and neuroregenerative approaches for white matter repair. However, less progress has been achieved in this area mainly due to the complexity and multifactorial nature of the degeneration processes. Here, we will provide a timely review on the current understanding of the cellular and molecular mechanisms of white matter degeneration and will also discuss recent pharmacological and cellular therapeutic approaches for white matter protection as well as axonal regeneration, oligodendrogenesis and remyelination.
脑白质退化是中枢神经系统的一种重要病理生理事件，其共同特征为脱髓鞘、少突胶质细胞丧失、轴突退化和实质改变，可导致感觉、运动、自主和认知障碍。脑白质退化可由多种原因引起，包括创伤、神经毒性暴露、血流不足、神经炎症以及发育性和遗传性神经病变。无论病因如何，退化过程具有相似的病理特征。近年来，已经确定了许多用于轴突和少突胶质细胞退化的细胞和分子机制，包括氧化损伤、钙超载、神经炎症事件、蛋白酶激活、三磷酸腺苷耗竭和能量供应不足。为了开发用于脑白质修复的神经保护和神经再生方法，已经进行了广泛的努力。然而，由于退化过程的复杂性和多因素性质，在这一领域取得的进展较少。在这里，我们将及时回顾脑白质退化的细胞和分子机制的最新认识，并讨论最近用于脑白质保护以及轴突再生、少突胶质细胞生成和髓鞘再生的药理学和细胞治疗方法。
