Naif H Ali, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Najah R Hadi, Abdullah A Assiri, Mohammed Alrouji, Nermeen N Welson, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha
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引用次数: 0
摘要
阿尔茨海默病(AD)是一种进行性神经退行性疾病,以记忆损伤和认知功能障碍为特征。研究表明,低血糖会对阿尔茨海默病的神经病理学产生不利影响。众所周知,2 型糖尿病(T2D)患者的慢性高血糖被认为是 AD 发生和发展的潜在风险因素。然而,以往的研究并未深入探讨复发性低血糖对AD发病机制的影响,也未从细胞和分子水平深入解读复发性低血糖如何影响AD。低血糖诱发AD的潜在机制多种多样,如内皮功能障碍、血栓形成、神经元损伤导致tau蛋白过度磷酸化和淀粉样β(Aβ)在大脑神经元中的积累。值得注意的是,控制血糖的胰高血糖素也能调节认知功能。胰高血糖素通过拮抗胰岛素的代谢作用来增加血糖。因此,胰高血糖素可通过减轻低血糖症来预防注意力缺失症的神经病理学。研究表明,胰高血糖素/GLP-1 可促进突触生成、海马突触可塑性以及学习和记忆,同时减轻淀粉样蛋白和 tau 病变。因此,激活大脑中的胰高血糖素受体可能会减轻 AD 的神经病理学。最近用于治疗低血糖症的胰高血糖素受体激动剂达西胰高血糖素可能会有效预防低血糖症和AD神经病理学。本综述旨在讨论达西胰高血糖素在治疗AD低血糖症中的潜在作用,以及这种药物如何减轻AD神经病理学。
Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aβ) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.
期刊介绍:
Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.