Department of Biochemistry, Neuroimmunology Group, Molecular Drug Metabolism and Toxicology Laboratory, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Division of Medical Sciences, Medical Sciences Building, University of Victoria, Victoria, BC, Canada.
Adv Neurobiol. 2024;37:497-512. doi: 10.1007/978-3-031-55529-9_27.
Neurodegenerative diseases are manifested by a progressive death of neural cells, resulting in the deterioration of central nervous system (CNS) functions, ultimately leading to specific behavioural and cognitive symptoms associated with affected brain regions. Several neurodegenerative disorders are caused by genetic variants or mutations, although the majority of cases are sporadic and linked to various environmental risk factors, with yet an unknown aetiology. Neuroglial changes are fundamental and often lead to the pathophysiology of neurodegenerative diseases. In particular, microglial cells, which are essential for maintaining CNS health, become compromised in their physiological functions with the exposure to environmental risk factors, genetic variants or mutations, as well as disease pathology. In this chapter, we cover the contribution of neuroglia, especially microglia, to several neurodegenerative diseases, including Nasu-Hakola disease, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, infectious disease-associated neurodegeneration, and metal-precipitated neurodegeneration. Future research perspectives for the field pertaining to the therapeutic targeting of microglia across these disease conditions are also discussed.
神经退行性疾病表现为神经细胞的进行性死亡,导致中枢神经系统 (CNS) 功能恶化,最终导致与受影响大脑区域相关的特定行为和认知症状。几种神经退行性疾病是由遗传变异或突变引起的,尽管大多数病例是散发性的,与各种环境风险因素有关,其病因尚不清楚。神经胶质的改变是基本的,往往导致神经退行性疾病的病理生理学。特别是小胶质细胞,对于维持中枢神经系统的健康至关重要,在暴露于环境风险因素、遗传变异或突变以及疾病病理过程中,其生理功能受到损害。在本章中,我们将介绍神经胶质,特别是小胶质细胞,对几种神经退行性疾病的贡献,包括 Nasu-Hakola 病、帕金森病、肌萎缩侧索硬化症、阿尔茨海默病、亨廷顿病、感染性疾病相关的神经退行性变和金属沉淀性神经退行性变。还讨论了该领域针对这些疾病条件下小胶质细胞的治疗靶向的未来研究展望。