Jones Michael K, Nair Archana, Gupta Mihir
Department of Medicine, Vascular Biology Center, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, United States.
Department of Ophthalmology, New York University, New York, NY, United States.
Front Cell Neurosci. 2019 Apr 30;13:171. doi: 10.3389/fncel.2019.00171. eCollection 2019.
Neurodegenerative diseases affect millions of people worldwide, yet there are currently no effective treatments. Because risk of neurodegenerative disease substantially increases with age, greater life expectancy with a concomitant aging population means more individuals will be affected in the coming decades. Thus, there is an urgent need for understanding the mechanisms driving neurodegenerative diseases in order to develop improved treatment strategies. Inflammation in the nervous system, termed "neuroinflammation," has become increasingly recognized as being associated with neurodegenerative diseases. Early attention focused primarily on morphological changes in astrocytes and microglia; however, brain and CNS resident mast cells are now receiving attention as a result of being "first responders" to injury. Mast cells also exert profound effects on their microenvironment and neighboring cells including behavior and/or activation of astrocytes, microglia, and neurons, which, in turn, are implicated in neuroinflammation, neurogenesis and neurodegeneration. Mast cells also affect disruption/permeability of the blood brain barrier enabling toxin and immune cell entry exacerbating an inflammatory microenvironment. Here, we discuss the roles of mast cells in neuroinflammation and neurodegeneration with a focus on development and progression of four prominent neurodegenerative diseases: Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Huntington's Disease.
神经退行性疾病影响着全球数百万人，但目前尚无有效的治疗方法。由于神经退行性疾病的风险会随着年龄的增长而大幅增加，预期寿命的延长以及随之而来的人口老龄化意味着在未来几十年里会有更多的人受到影响。因此，迫切需要了解导致神经退行性疾病的机制，以便制定更好的治疗策略。神经系统中的炎症，即“神经炎症”，已越来越多地被认为与神经退行性疾病有关。早期的研究主要集中在星形胶质细胞和小胶质细胞的形态变化上；然而，由于脑和中枢神经系统驻留肥大细胞是损伤的“第一反应者”，现在它们也受到了关注。肥大细胞还对其微环境和邻近细胞产生深远影响，包括星形胶质细胞、小胶质细胞和神经元的行为和/或激活，而这些细胞又与神经炎症、神经发生和神经退行性变有关。肥大细胞还会影响血脑屏障的破坏/通透性，使毒素和免疫细胞进入，从而加剧炎症微环境。在这里，我们将讨论肥大细胞在神经炎症和神经退行性变中的作用，重点关注四种主要神经退行性疾病：阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿舞蹈病的发展和进展。
