German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127, Bonn, Germany; Institute of Innate Immunity, University Hospital Bonn, Bonn, Germany.
Institute of Innate Immunity, University Hospital Bonn, Bonn, Germany; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, 7491, Trondheim, Norway; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01605, USA; Deutsches Rheuma-Forschungszentrum (DRFZ), Charitéplatz 1, 10117, Berlin, Germany.
Neuropharmacology. 2024 Jul 1;252:109941. doi: 10.1016/j.neuropharm.2024.109941. Epub 2024 Mar 31.
Every year, 10 million people develop dementia, the most common of which is Alzheimer's disease (AD). To date, there is no way to prevent cognitive decline and therapies are limited. This review provides a neuroimmunological perspective on the progression of AD, and discusses the immune-targeted therapies that are in preclinical and clinical trials that may impact the development of this disease. Specifically, we look to the role of the NLRP3 inflammasome, its triggers in the brain and how its activation can contribute to the progression of dementia. We summarise the range of inhibitors targeting the NLRP3 inflammasome and its downstream pathways that are under investigation, and discuss future therapeutic perspectives for this devastating condition.
每年有 1000 万人患有痴呆症,其中最常见的是阿尔茨海默病(AD)。迄今为止,尚无预防认知能力下降的方法,而且疗法有限。本综述从神经免疫学角度探讨了 AD 的进展,并讨论了正在进行临床前和临床试验的免疫靶向疗法,这些疗法可能会影响该疾病的发展。具体而言,我们研究了 NLRP3 炎性小体的作用、其在大脑中的触发因素以及其激活如何促进痴呆症的发展。我们总结了正在研究的针对 NLRP3 炎性小体及其下游途径的各种抑制剂,并讨论了针对这种破坏性疾病的未来治疗前景。