Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
Chem Soc Rev. 2014 Oct 7;43(19):6672-82. doi: 10.1039/c4cs00005f. Epub 2014 Apr 8.
Cholesterol and metal ions have been suggested to be associated with the onset and progression of Alzheimer's disease (AD). Moreover, recent findings have demonstrated a potential interconnection between these two factors. For example, (a) cholesterol has been shown to be misregulated in AD-afflicted brains, and the aberrant activity of proteins (particularly, apolipoprotein E (ApoE) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)) has been linked to cholesterol-related AD exacerbation; (b) dyshomeostasis of metal ions associated with misfolded proteins (i.e., amyloid-β (Aβ) aggregates) found in the brains of AD patients is shown to promote oxidative stress leading to the malfunction of multiple proteins, including cytochrome c oxidase (CcO), and Cu/Zn superoxide dismutase (SOD1); (c) metal ion misregulation has also been observed to disrupt the activity of proteins (e.g., HMGR, low-density lipoproteins (LDL)), required for cholesterol production and regulation. Herein, we briefly discuss the potential involvement of cholesterol and metal ions in AD neuropathogenesis in both individual and interrelated manners.
胆固醇和金属离子被认为与阿尔茨海默病（AD）的发病和进展有关。此外，最近的研究结果表明这两个因素之间存在潜在的联系。例如：(a) 在受 AD 影响的大脑中，胆固醇的调节出现异常，并且蛋白质的异常活性（特别是载脂蛋白 E (ApoE) 和 3-羟-3-甲基戊二酰辅酶 A (HMG-CoA) 还原酶 (HMGR)）与胆固醇相关的 AD 恶化有关；(b) AD 患者大脑中与错误折叠蛋白质（即淀粉样蛋白-β (Aβ) 聚集体）相关的金属离子的动态平衡失调，被证明会促进氧化应激，导致包括细胞色素 c 氧化酶 (CcO) 和铜/锌超氧化物歧化酶 (SOD1) 在内的多种蛋白质的功能障碍；(c) 金属离子的失调也被观察到会破坏胆固醇产生和调节所需的蛋白质（例如 HMGR、低密度脂蛋白 (LDL)）的活性。本文简要讨论了胆固醇和金属离子在 AD 神经发病机制中的个体和相互关联的潜在作用。
