Departments of Medicine (Neurology) and Chemistry, Krembil Research Institute, University Health Network, University of Toronto, Toronto, 60 Leonard Avenue, ON, Canada M5T 0S8.
Curr Alzheimer Res. 2023;20(2):63-70. doi: 10.2174/1567205020666230517103312.
Beyond the time-honoured targeting of protein misfolding and aggregation, Alzheimer's disease needs new, innovative therapeutic directions. When exploring alternative druggable mechanisms, multifaceted in vitro and in vivo data demonstrate that immune system dysfunction is a pivotal driver of Alzheimer's disease progression. In pursuing neuroimmunological targets, a major but often under-discussed consideration regards the issue of whether innate or adaptive immunity (or both) within the neuroimmune network should be the centre of focus when devising immunotherapeutic approaches to Alzheimer's. This perspective article briefly reviews current data, concluding that while both innate and adaptive immunity contributes to the immunopathology of Alzheimer's, the proinflammatory microglia and cytokines of innate immunity will provide higher yield targets with a greater likelihood of efficacy. Although it seems paradoxical to focus on a rapid, short-lived aspect of immunity when seeking approaches to a quintessentially chronic brain disease, accumulating evidence affords ample data to support the target-rich cascade of innate immunity for the development of much-needed new diagnostics and therapeutics.
除了传统的靶向蛋白质错误折叠和聚集外，阿尔茨海默病还需要新的、创新的治疗方向。在探索替代的可药物治疗机制时，多方面的体外和体内数据表明，免疫系统功能障碍是阿尔茨海默病进展的关键驱动因素。在追求神经免疫靶点时，一个主要但经常被忽视的考虑因素是，在设计针对阿尔茨海默病的免疫治疗方法时，神经免疫网络中的固有免疫还是适应性免疫（或两者）应该成为关注的焦点。本文简要回顾了现有数据，得出的结论是，尽管固有免疫和适应性免疫都有助于阿尔茨海默病的免疫病理学，但促炎小胶质细胞和细胞因子的固有免疫将为更有可能有效的治疗提供更高的靶点产量。虽然当寻求治疗一种典型的慢性脑部疾病的方法时，专注于免疫的快速、短暂方面似乎有些矛盾，但越来越多的证据提供了充足的数据来支持固有免疫的靶向丰富级联反应，以开发急需的新诊断和治疗方法。
