Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, TX, USA.
Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, TX, USA.
Ageing Res Rev. 2022 Jun;78:101637. doi: 10.1016/j.arr.2022.101637. Epub 2022 Apr 30.
Strategies proficient for relieving cognitive impairments in aging and Alzheimer's disease (AD) have an enormous impact. Regular physical exercise (PE) can prevent age-related dementia and slow down AD progression. However, such a lifestyle change is likely not achievable for individuals displaying age-related frailty. Hence, drugs or biologics that could simulate the benefits of PE have received much attention. Previous studies suggested that the fibronectin-domain III containing 5 (FNDC5) underlies the PE-mediated improved cognitive function. A recent study reports that PE-related cognitive benefits in aging and AD are mediated by irisin, the cleaved form of FNDC5 released into the blood after PE. Such a conclusion was apparent from the deletion of irisin through a global knockout of FNDC5, leading to the loss of PE-induced cognitive benefits or inducing memory impairments in adult or aged models. Furthermore, in AD models, peripherally administered irisin mimicked the cognitive benefits of PE by modulating neuroinflammation. This short review discusses the promise of irisin to simulate the cognitive benefits of PE in age- and AD-related dementia. In addition, critical issues such as how blood-borne irisin acts on neural cells, the role of the brain-derived neurotrophic factor in irisin-mediated cognitive benefits, and irisin's ability to inhibit neuroinflammatory cascades in aging and AD are discussed.
缓解衰老和阿尔茨海默病（AD）认知障碍的策略有很大的影响。有规律的体育锻炼（PE）可以预防与年龄相关的痴呆症，并减缓 AD 的进展。然而，对于表现出与年龄相关的脆弱性的个体来说，这种生活方式的改变可能是不可能的。因此，能够模拟 PE 益处的药物或生物制剂受到了广泛关注。先前的研究表明，纤维连接蛋白结构域 III 包含 5（FNDC5）是 PE 介导的认知功能改善的基础。最近的一项研究报告称，PE 相关的认知益处是由 FNDC5 释放到血液中的裂解形式鸢尾素介导的。通过 FNDC5 的全局敲除来删除鸢尾素，导致 PE 诱导的认知益处丧失或在成年或老年模型中诱导记忆损伤，这一结论显而易见。此外，在 AD 模型中，外周给予鸢尾素通过调节神经炎症模拟 PE 的认知益处。这篇简短的综述讨论了鸢尾素模拟 PE 在与年龄和 AD 相关的痴呆中的认知益处的潜力。此外，还讨论了一些关键问题，如血液中鸢尾素如何作用于神经细胞、脑源性神经营养因子在鸢尾素介导的认知益处中的作用以及鸢尾素抑制衰老和 AD 中神经炎症级联的能力。
