Kim Eunhee, Tanzi Rudolph E, Choi Se Hoon
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Neural Regen Res. 2025 Jun 1;20(6):1555-1564. doi: 10.4103/NRR.NRR-D-24-00098. Epub 2024 Jul 10.
Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.
鸢尾素是一种肌动蛋白，它是由膜蛋白含III型纤连蛋白结构域蛋白5（FNDC5）在体育锻炼时裂解产生的。研究表明，在阿尔茨海默病（老年人中最常见的痴呆形式）的细胞培养或动物模型中，鸢尾素/FNDC5通过改善认知功能、减少淀粉样β蛋白和tau蛋白病变以及神经炎症，对阿尔茨海默病具有神经保护作用。尽管目前对鸢尾素/FNDC5的研究显示出了有前景的结果，但仍需要进一步的机制研究来阐明其作为缓解阿尔茨海默病的有意义治疗靶点的潜力。我们最近发现，鸢尾素治疗可通过增加星形胶质细胞分泌的淀粉样β蛋白降解酶中性内肽酶的活性/水平来减少淀粉样β蛋白病变。在此，我们概述了鸢尾素/FNDC5对阿尔茨海默病的保护作用和机制。
