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脂蛋白代谢、蛋白质聚集与阿尔茨海默病:文献综述

Lipoprotein Metabolism, Protein Aggregation, and Alzheimer's Disease: A Literature Review.

机构信息

Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, 41009 Sevilla, Spain.

Department of Pharmacology, Pediatrics, and Radiology, School of Medicine, University of Seville, 41009 Sevilla, Spain.

出版信息

Int J Mol Sci. 2023 Feb 2;24(3):2944. doi: 10.3390/ijms24032944.

Abstract

Alzheimer's disease (AD) is the most common form of dementia. The physiopathology of AD is well described by the presence of two neuropathological features: amyloid plaques and tau neurofibrillary tangles. In the last decade, neuroinflammation and cellular stress have gained importance as key factors in the development and pathology of AD. Chronic cellular stress occurs in degenerating neurons. Stress Granules (SGs) are nonmembranous organelles formed as a response to stress, with a protective role; however, SGs have been noted to turn into pathological and neurotoxic features when stress is chronic, and they are related to an increased tau aggregation. On the other hand, correct lipid metabolism is essential to good function of the brain; apolipoproteins are highly associated with risk of AD, and impaired cholesterol efflux and lipid transport are associated with an increased risk of AD. In this review, we provide an insight into the relationship between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.

摘要

阿尔茨海默病(AD)是最常见的痴呆症形式。AD 的病理生理学通过存在两种神经病理学特征得到了很好的描述:淀粉样斑块和 tau 神经原纤维缠结。在过去的十年中,神经炎症和细胞应激已成为 AD 发展和病理学的关键因素。慢性细胞应激发生在退化的神经元中。应激颗粒(SGs)是在应激反应下形成的非膜性细胞器,具有保护作用;然而,当应激是慢性时,SGs 已被注意到变成病理性和神经毒性特征,并且它们与 tau 聚集增加有关。另一方面,正确的脂质代谢对于大脑的良好功能至关重要;载脂蛋白与 AD 的风险高度相关,胆固醇外排和脂质转运受损与 AD 的风险增加有关。在这篇综述中,我们深入探讨了 AD 中细胞应激、SGs、蛋白质聚集和脂质代谢之间的关系。

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