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糖尿病患者的阿尔茨海默病:脂质组学展望。

Alzheimer's Disease in Diabetic Patients: A Lipidomic Prospect.

机构信息

School of Medicine, Tehran University of Medical Sciences, Iran.

School of Medicine, Tehran University of Medical Sciences, Iran.

出版信息

Neuroscience. 2023 Oct 15;530:79-94. doi: 10.1016/j.neuroscience.2023.08.033. Epub 2023 Aug 29.

Abstract

Diabetes Mellitus (DM) and Alzheimer's disease (AD) have been two of the most common chronic diseases affecting people worldwide. Type 2 DM (T2DM) is a metabolic disease depicted by insulin resistance, dyslipidemia, and chronic hyperglycemia while AD is a neurodegenerative disease marked by Amyloid β (Aβ) accumulation, neurofibrillary tangles aggregation, and tau phosphorylation. Various clinical, epidemiological, and lipidomics studies have linked those diseases claiming shared pathological pathways raising the assumption that diabetic patients are at an increased risk of developing AD later in their lives. Insulin resistance is the tipping point beyond where advanced glycation end (AGE) products and free radicals are produced leading to oxidative stress and lipid peroxidation. Additionally, different types of lipids are playing a crucial role in the development and the relationship between those diseases. Lipidomics, an analysis of lipid structure, formation, and interactions, evidently exhibits these lipid changes and their direct and indirect effect on Aβ synthesis, insulin resistance, oxidative stress, and neuroinflammation. In this review, we have discussed the pathophysiology of T2DM and AD, the interconnecting pathological pathways they share, and the lipidomics where different lipids such as cholesterol, phospholipids, sphingolipids, and sulfolipids contribute to the underlying features of both diseases. Understanding their role can be beneficial for diagnostic purposes or introducing new drugs to counter AD.

摘要

糖尿病(DM)和阿尔茨海默病(AD)一直是全球范围内影响人们的两种最常见的慢性疾病。2 型糖尿病(T2DM)是一种代谢疾病,其特征为胰岛素抵抗、血脂异常和慢性高血糖,而 AD 是一种神经退行性疾病,其特征为淀粉样β(Aβ)积聚、神经原纤维缠结聚集和 tau 磷酸化。各种临床、流行病学和脂质组学研究将这些疾病联系起来,声称它们具有共同的病理途径,这使得人们假设糖尿病患者在以后的生活中患 AD 的风险增加。胰岛素抵抗是导致晚期糖基化终产物(AGE)产物和自由基产生的临界点,从而导致氧化应激和脂质过氧化。此外,不同类型的脂质在这些疾病的发展和关系中起着至关重要的作用。脂质组学是一种分析脂质结构、形成和相互作用的方法,显然可以显示这些脂质变化及其对 Aβ合成、胰岛素抵抗、氧化应激和神经炎症的直接和间接影响。在这篇综述中,我们讨论了 T2DM 和 AD 的病理生理学、它们共同的病理途径以及脂质组学,不同的脂质,如胆固醇、磷脂、鞘脂和硫酸脂,对这两种疾病的潜在特征都有贡献。了解它们的作用有助于诊断目的或引入新的药物来对抗 AD。

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