穿越交叉点:糖尿病与阿尔茨海默氏症的交织关系。

IF 12.5 1区 医学 Q1 CELL BIOLOGY Ageing Research Reviews Pub Date : 2024-07-14 DOI:10.1016/j.arr.2024.102415
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引用次数: 0

摘要

阿尔茨海默病(AD)和糖尿病(DM)表现出相似的病理生理途径。APP、PS-1和PS-2的基因异常与阿尔茨海默病有关,脑脊液和血液中的生物标志物有助于诊断。胰岛素功能障碍在 AD 中被称为 "3 型糖尿病",涉及胰岛素信号的改变和神经元的萎缩。胰岛素会影响β-淀粉样蛋白的代谢,加剧AD的神经毒性和DM的淀粉样蛋白生成。这两种疾病都会导致葡萄糖转运体表达受损,从而加速认知能力的衰退。线粒体功能障碍和 Toll 样受体 4 介导的炎症会加重这两种疾病的神经退行性变。载脂蛋白E4会增加患病风险,尤其是在糖尿病中常见的血脂异常的情况下。针对胰岛素降解酶活化和 HSP60 等共同途径进行治疗干预是有希望的。认识到这些相互关联的机制强调了开发针对AD和DM重叠病理生理学的定制治疗方法的必要性,为更有效地治疗这两种疾病提供了潜在的途径。
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Navigating the intersection: Diabetes and Alzheimer's intertwined relationship

Alzheimer's disease (AD) and Diabetes mellitus (DM) exhibit comparable pathophysiological pathways. Genetic abnormalities in APP, PS-1, and PS-2 are linked to AD, with diagnostic aid from CSF and blood biomarkers. Insulin dysfunction, termed "type 3 diabetes mellitus" in AD, involves altered insulin signalling and neuronal shrinkage. Insulin influences beta-amyloid metabolism, exacerbating neurotoxicity in AD and amyloid production in DM. Both disorders display impaired glucose transporter expression, hastening cognitive decline. Mitochondrial dysfunction and Toll-like receptor 4-mediated inflammation worsen neurodegeneration in both diseases. ApoE4 raises disease risk, especially when coupled with dyslipidemia common in DM. Targeting shared pathways like insulin-degrading enzyme activation and HSP60 holds promise for therapeutic intervention. Recognizing these interconnected mechanisms underscores the imperative for developing tailored treatments addressing the overlapping pathophysiology of AD and DM, offering potential avenues for more effective management of both conditions.

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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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