Multifactorial glial responses and their contributions to Alzheimer's disease continuum
Multifactorial glial responses and their contributions to Alzheimer's disease continuum
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DOI：
10.1111/cen3.12745
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发表时间：
2023-02
影响因子：
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通讯作者：
Masanori Hijioka;T. Manabe;T. Saito
中科院分区：
文献类型：
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作者：
Masanori Hijioka;T. Manabe;T. Saito
阿尔茨海默病（AD）是最常见的神经认知障碍。在临床症状出现之前，各种因素错综复杂地交织在一起，尽管淀粉样蛋白β肽沉积和神经原纤维缠结形成（即阿尔茨海默病大脑的病理标志）都是确定的。在这些因素中，神经胶质反应越来越被认为是这些病理进展中的重要角色，并被视为AD连续体的一个组成部分。然而，阿尔茨海默病发病机制中胶质细胞功能的详细分子和细胞机制仍有待阐明。最近的研究表明，外周免疫、肠道微生物群或环境因素通过与脑胶质细胞的交流影响脑病理生理。这种疾病的复杂性使得了解阿尔茨海默病的病因变得困难，并阻碍了有效治疗策略的发展，以应对这种疾病。相反，老年患者往往患有多种疾病，而不是单一疾病，AD的发病机制可能与其他疾病引起的病理有关。因此，将AD作为一种全身性疾病进行研究对于确定治疗干预措施至关重要。本文综述了阿尔茨海默病的研究现状，并就阿尔茨海默病的病理生理方面的神经胶质功能的认识进行了综述。
Alzheimer's disease (AD) is the most common neurocognitive disorder. Various factors are intricately intertwined before clinical symptoms appear, although both amyloid‐β peptide deposition and neurofibrillary tangle formation (i.e. pathological hallmarks of the AD brain) are established. Among such factors, glial responses have been increasingly recognized as important roles in the progression of these pathologies and viewed as one component of the AD continuum. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain to be elucidated. Recent studies showed that peripheral immunity, gut microbiota or environmental factors influence brain pathophysiologies through communication with glial cells in the brain. This disease complexity makes understanding AD etiology difficult and hinders the development of effective therapeutic strategies to tackle this disease. Conversely, aged patients often suffer from multiple – not a single – diseases as multimorbidity, and AD pathogenesis might be related to pathologies caused by other diseases. Hence, investigating AD as a systemic disease has become critical for identifying therapeutic interventions. This review aimed to summarize current knowledge on AD research and share perspectives for understanding glial functions regarding AD pathophysiology.