Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2020 Jul 22;11:1574. doi: 10.3389/fimmu.2020.01574. eCollection 2020.
Age-dependent neurodegenerative disorders are a set of diseases that affect millions of individuals worldwide. Apart from a small subset that are the result of well-defined inherited autosomal dominant gene mutations (e.g., those encoding the β-amyloid precursor protein and presenilins), our understanding of the genetic network that underscores their pathology, remains scarce. Genome-wide association studies (GWAS) especially in Alzheimer's disease patients and research in Parkinson's disease have implicated inflammation and the innate immune response as risk factors. However, even if GWAS etiology points toward innate immunity, untangling cause, and consequence is a challenging task. Specifically, it is not clear whether predisposition to de-regulated immunity causes an inadequate response to protein aggregation (such as amyloid or α-synuclein) or is the direct cause of this aggregation. Given the evolutionary conservation of the innate immune response in and humans, unraveling whether hyperactive immune response in glia have a protective or pathological role in the brain could be a potential strategy in combating age-related neurological diseases.
年龄相关性神经退行性疾病是一组影响全球数百万人的疾病。除了一小部分是由明确的常染色体显性基因突变引起的（例如，那些编码β-淀粉样前体蛋白和早老素的基因），我们对其病理学基础的遗传网络的理解仍然很少。全基因组关联研究（GWAS），特别是在阿尔茨海默病患者中的研究和帕金森病的研究表明，炎症和先天免疫反应是风险因素。然而，即使 GWAS 的病因指向先天免疫，理清因果关系仍然是一项具有挑战性的任务。具体来说，尚不清楚对调节免疫的易感性是否导致对蛋白质聚集（如淀粉样蛋白或α-突触核蛋白）的反应不足，还是这种聚集的直接原因。鉴于先天免疫反应在 和人类中具有进化上的保守性，阐明胶质细胞中过度活跃的免疫反应在大脑中是具有保护作用还是病理性作用，可能是对抗与年龄相关的神经退行性疾病的一种潜在策略。
