Department of Neurology and Neurophysiology, Liverpool Hospital, Sydney, New South Wales, Australia; Stroke and Neurology Research Group, Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia.
Department of Endocrinology, Changzhou No.2 People's Hospital, Nanjing Medical University, Changzhou, China.
Pharmacol Ther. 2020 Aug;212:107559. doi: 10.1016/j.pharmthera.2020.107559. Epub 2020 May 5.
The linkage of neurodegenerative diseases with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), including oxidative stress, mitochondrial dysfunction, excessive inflammatory responses and abnormal protein processing, and the correlation between cerebrovascular diseases and hyperglycemia has opened a new window for novel therapeutics for these cognitive disorders. Various antidiabetic agents have been studied for their potential treatment of cognitive disorders, among which the dipeptidyl peptidase-4 (DPP-4) inhibitors have been investigated more recently. So far, DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models, and cognitive benefits in diabetic patients with or without cognitive impairments. This review aims to summarize the potential mechanisms, advantages and limitations, and currently available evidence for developing DPP-4 inhibitors as a treatment of cognitive disorders.
神经退行性疾病与胰岛素抵抗(IR)和 2 型糖尿病(T2DM)的关联,包括氧化应激、线粒体功能障碍、过度炎症反应和异常蛋白处理,以及脑血管疾病与高血糖之间的相关性,为这些认知障碍的新疗法开辟了新的途径。各种抗糖尿病药物已被研究用于治疗认知障碍,其中二肽基肽酶-4(DPP-4)抑制剂最近受到了更多的关注。到目前为止,DPP-4 抑制剂已在动物模型中显示出神经保护和认知改善作用,并在有或没有认知障碍的糖尿病患者中显示出认知益处。本综述旨在总结开发 DPP-4 抑制剂作为治疗认知障碍的潜在机制、优势和局限性以及现有证据。