Kaur Parneet, Khan Heena, Grewal Amarjot Kaur, Dua Kamal, Singh Sachin Kumar, Gupta Gaurav, Singh Thakur Gurjeet
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, 140401, Punjab, India.
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia.
CNS Neurol Disord Drug Targets. 2025;24(3):196-207. doi: 10.2174/0118715273321002240919102841.
Alzheimer's disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world's population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders.
阿尔茨海默病是一种与脑细胞退化相关的疾病,这种疾病是痴呆症的主要病因。代谢应激通过FOXO信号通路影响阿尔茨海默病患者大脑的活动。随着世界人口老龄化以及近几十年来生活方式的改变,阿尔茨海默病的发病率将显著飙升,这表明生活方式的改变是发病率上升的主要原因。同样,目前成年人的代谢紊乱,如肥胖、中风和糖尿病,已被视为阿尔茨海默病的风险因素。环境影响会诱发基因突变,从而导致多种疾病的发生。当个体暴露在食物容易获取且能量消耗极少的环境中时,就会出现代谢紊乱。肥胖和糖尿病是全球最主要的健康问题。肥胖是由于能量摄入与能量消耗之间的不平衡所致,这是由行为和生理因素共同引起的。肥胖、胰岛素抵抗综合征、高血压和炎症是导致全球患糖尿病和神经退行性疾病风险增加的因素。FOXO转录因子是保守分子,在各种生物学过程中发挥重要作用,尤其是在衰老和代谢过程中。细胞凋亡、细胞分裂与分化、氧化应激、代谢和寿命等生理过程都在FOXO蛋白的调控范围内。在本综述中,我们探讨了信号通路与FOXO蛋白细胞功能之间的相关性。我们还总结了FOXO在阿尔茨海默病中的复杂作用,重点关注代谢应激,并讨论了FOXO作为阿尔茨海默病与代谢紊乱之间分子联系所具有的前景。