Weiner Howard L
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Neurol. 2025 Feb;21(2):67-85. doi: 10.1038/s41582-024-01046-7. Epub 2024 Dec 16.
The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role. Immunotherapeutic approaches that target the adaptive and innate immune systems are being explored for the treatment of almost all neurological diseases, and the targets and approaches are often common across diseases. Microglia are the primary immune cells in the brain that contribute to disease pathogenesis, and are consequently a common immune target for therapy. Other therapeutic approaches target components of the peripheral immune system, such as regulatory T cells and monocytes, which in turn act within the CNS. This Review considers in detail how microglia, monocytes and T cells contribute to the pathogenesis of multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, and their potential as shared therapeutic targets across these diseases. The microbiome is also highlighted as an emerging therapeutic target that indirectly modulates the immune system. Therapeutic approaches being developed to target immune function in neurodegenerative diseases are discussed, highlighting how immune-based approaches developed to treat one disease could be applicable to multiple other neurological diseases.
免疫系统在神经退行性疾病中起主要作用。在某些疾病中，如多发性硬化症，它是疾病的主要驱动因素。在其他疾病中，如阿尔茨海默病、肌萎缩侧索硬化症和帕金森病，它具有放大作用。针对适应性和先天性免疫系统的免疫治疗方法正在被探索用于治疗几乎所有的神经疾病，而且这些靶点和方法在不同疾病中常常是相同的。小胶质细胞是大脑中导致疾病发病机制的主要免疫细胞，因此是常见的治疗免疫靶点。其他治疗方法针对外周免疫系统的组成部分，如调节性T细胞和单核细胞，它们进而在中枢神经系统内发挥作用。本综述详细探讨了小胶质细胞、单核细胞和T细胞如何促成多发性硬化症、阿尔茨海默病、肌萎缩侧索硬化症和帕金森病的发病机制，以及它们作为这些疾病共同治疗靶点的潜力。微生物群也被视为一个新兴的治疗靶点，它可间接调节免疫系统。本文讨论了为针对神经退行性疾病中的免疫功能而开发的治疗方法，强调了为治疗一种疾病而开发的基于免疫的方法如何可能适用于多种其他神经疾病。
