最多等待 10 秒，若超时请稍后重试。
Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam University Medical Center, Amsterdam, Netherlands.
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, Netherlands.
Front Aging Neurosci. 2021 Jun 24;13:690372. doi: 10.3389/fnagi.2021.690372. eCollection 2021.
While the central nervous system compromises 2% of our body weight, it harbors up to 25% of the body's cholesterol. Cholesterol levels in the brain are tightly regulated for physiological brain function, but mounting evidence indicates that excessive cholesterol accumulates in Alzheimer's disease (AD), where it may drive AD-associated pathological changes. This seems especially relevant for late-onset AD, as several of the major genetic risk factors are functionally associated with cholesterol metabolism. In this review we discuss the different systems that maintain brain cholesterol metabolism in the healthy brain, and how dysregulation of these processes can lead, or contribute to, Alzheimer's disease. We will also discuss how AD-risk genes might impact cholesterol metabolism and downstream AD pathology. Finally, we will address the major outstanding questions in the field and how recent technical advances in CRISPR/Cas9-gene editing and induced pluripotent stem cell (iPSC)-technology can aid to study these problems.
虽然中枢神经系统仅占我们体重的2%，但其所含胆固醇却高达人体胆固醇总量的25%。大脑中的胆固醇水平受到严格调控以维持大脑的生理功能，但越来越多的证据表明，在阿尔茨海默病（AD）中会积累过多的胆固醇，这可能会引发与AD相关的病理变化。这一点在晚发性AD中似乎尤为重要，因为一些主要的遗传风险因素在功能上与胆固醇代谢相关。在这篇综述中，我们讨论了在健康大脑中维持脑胆固醇代谢的不同系统，以及这些过程的失调如何导致或促成阿尔茨海默病。我们还将讨论AD风险基因如何影响胆固醇代谢和下游的AD病理。最后，我们将阐述该领域主要的悬而未决的问题，以及CRISPR/Cas9基因编辑和诱导多能干细胞（iPSC）技术的最新技术进展如何有助于研究这些问题。
