Millions of people are affected by neurodegenerative diseases worldwide. They occur due to the loss of brain functions or peripheral nervous system dysfunction. If untreated, prolonged condition ultimately leads to death. Mostly they are associated with stress, altered cholesterol metabolism, inflammation and organelle dysfunction. Endogenous cholesterol and phospholipids in brain undergo auto-oxidation by enzymatic as well as non-enzymatic modes leading to the formation of by-products such as 4-hydroxynonenal and oxysterols. Among various oxysterols, 7-ketocholesterol (7KCh) is one of the major toxic components involved in altering neuronal lipid metabolism, contributing to inflammation and nerve cell damage. More evidently 7KCh is proven to induce oxidative stress and affects membrane permeability. Loss in mitochondrial membrane potential affects metabolism of cell organelles such as lysosomes and peroxisomes which are involved in lipid and protein homeostasis. This in turn could affect amyloidogenesis, tau protein phosphorylation and accumulation in pathological conditions of neurodegenerative diseases. Lipid alterations and the consequent pathogenic protein accumulation, results in the damage of cell organelles and microglial cells. This could be a reason behind disease progression and predominantly reported characteristics of neurodegenerative disorders such as Alzheimer’s disease. This review focuses on the role of 7KCh mediated neurodegenerative Alzheimer’s disease with emphasis on alterations in the lipid raft microdomain. In addition, current trends in the significant therapies related to 7KCh inhibition are highlighted.

全世界有数百万人受到神经退行性疾病的影响。它们是由于大脑功能丧失或周围神经系统功能障碍而发生的。如果不及时治疗，长期病情最终会导致死亡。它们大多与压力、胆固醇代谢改变、炎症和细胞器功能障碍有关。大脑中的内源性胆固醇和磷脂通过酶促和非酶促模式进行自动氧化，导致形成 4-羟基壬烯醛和氧甾醇等副产物。在各种氧甾醇中，7-酮胆固醇 (7KCh) 是参与改变神经元脂质代谢、导致炎症和神经细胞损伤的主要有毒成分之一。更明显的是，7KCh 被证明会诱导氧化应激并影响膜通透性。线粒体膜电位的丧失会影响细胞器的代谢，例如参与脂质和蛋白质稳态的溶酶体和过氧化物酶体。这反过来又可能影响神经退行性疾病病理条件下的淀粉样蛋白生成、tau 蛋白磷酸化和积累。脂质改变和随之而来的致病蛋白积累，导致细胞器和小胶质细胞的损伤。这可能是疾病进展背后的原因，也是阿尔茨海默病等神经退行性疾病的主要报道特征。本综述重点关注 7KCh 介导的神经退行性阿尔茨海默病的作用，重点是脂筏微区的改变。此外，还强调了与 7KCh 抑制相关的重要疗法的当前趋势。