2 型糖尿病/肥胖症药物:神经退行性疾病的救星还是遥不可及的桥梁?
Type 2 diabetes mellitus/obesity drugs: A neurodegenerative disorders savior or a bridge too far?
机构信息
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
出版信息
Ageing Res Rev. 2024 Jul;98:102343. doi: 10.1016/j.arr.2024.102343. Epub 2024 May 16.
Glucagon-like peptide-1 (GLP-1) receptor agonist-based drugs (incretin mimetics) have meaningfully impacted current treatment of type 2 diabetes mellitus (T2DM), and their actions on satiety and weight loss have led to their use as an obesity medication. With multiple pleotropic actions beyond their insulinotropic and weight loss ones, including anti-inflammatory and anti-insulin-resistant effects selectively mediated by their receptors present within numerous organs, this drug class offers potential efficacy for an increasing number of systemic and neurological disorders whose current treatment is inadequate. Among these are a host of neurodegenerative disorders that are prevalent in the elderly, such as Parkinson's and Alzheimer's disease, which have bucked previous therapeutic approaches. An increasing preclinical, clinical, and epidemiological literature suggests that select incretin mimetics may provide an effective treatment strategy, but 'which ones' for 'which disorders' and 'when' remain key open questions.
胰高血糖素样肽-1(GLP-1)受体激动剂类药物(肠促胰岛素类似物)对 2 型糖尿病(T2DM)的当前治疗产生了重大影响,其对饱腹感和体重减轻的作用促使它们被用作肥胖症药物。除了其胰岛素分泌和减肥作用之外,它们还有多种多效性作用,包括通过其在众多器官中存在的受体选择性介导的抗炎和抗胰岛素抵抗作用,这类药物为越来越多的当前治疗方法不足的系统性和神经退行性疾病提供了潜在的疗效。其中包括许多在老年人中流行的神经退行性疾病,如帕金森病和阿尔茨海默病,这些疾病此前的治疗方法都未能奏效。越来越多的临床前、临床和流行病学文献表明,某些肠促胰岛素类似物可能提供有效的治疗策略,但“哪些药物”用于“哪些疾病”以及“何时”仍存在关键的未解决问题。