Abstract：
Significance: Cholesterol plays a crucial role in the brain, where it is highly concentrated and tightly regulated to support normal brain functions. It serves as a vital component of cell membranes, ensuring their integrity, and acts as a key regulator of various brain processes. Dysregulation of cholesterol metabolism in the brain has been linked to impaired brain function and the onset of neurodegenerative diseases such as Alzheimer\'s disease (AD), Parkinson\'s disease, and Huntington\'s disease. Recent Advances: A significant advancement has been the identification of astrocyte-derived apoliprotein E as a key regulator of de novo cholesterol biosynthesis in neurons, providing insights into how extracellular signals influence neuronal cholesterol levels. In addition, the development of antibody-based therapies, particularly for AD, presents promising opportunities for therapeutic interventions. Critical Issues: Despite significant research, the association between cholesterol and neurodegenerative diseases remains inconclusive. It is crucial to distinguish between plasma cholesterol and brain cholesterol, as these pools are relatively independent. This differentiation should be considered when evaluating statin-based treatment approaches. Furthermore, assessing not only the total cholesterol content in the brain but also its distribution among different types of brain cells is essential. Future Direction: Establishing a causal link between changes in brain/plasma cholesterol levels and the onset of brain dysfunction/neurodegenerative diseases remains a key objective. In addition, conducting cell-specific analyses of cholesterol homeostasis in various types of brain cells under pathological conditions will enhance our understanding of cholesterol metabolism in neurodegenerative diseases. Manipulating cholesterol levels to restore homeostasis may represent a novel approach for alleviating neurological symptoms.
摘要：
结论：胆固醇在大脑中起着至关重要的作用，它高度集中并受到严格调节以支持正常的大脑功能。它是细胞膜的重要组成部分，确保他们的完整性，并充当各种大脑过程的关键调节器。大脑中胆固醇代谢失调与脑功能受损和神经退行性疾病如阿尔茨海默病（AD）的发作有关。帕金森病（PD），和亨廷顿病（HD）。
背景：一个重大进展是将星形胶质细胞衍生的ApoE鉴定为神经元从头胆固醇生物合成的关键调节剂，提供有关细胞外信号如何影响神经元胆固醇水平的见解。此外,基于抗体的疗法的发展，特别是对于AD,为治疗干预提供了有希望的机会。
结果：尽管进行了大量研究，胆固醇和神经退行性疾病之间的关系仍然没有定论。区分血浆胆固醇和脑胆固醇至关重要，因为这些池相对独立。在评估基于他汀类药物的治疗方法时，应考虑这种差异。不仅要评估大脑中的总胆固醇含量，还要评估其在不同类型脑细胞中的分布。
结论：建立脑/血浆胆固醇水平变化与脑功能障碍/神经退行性疾病发病之间的因果关系仍然是一个关键目标。此外,在病理条件下对各种类型的脑细胞中的胆固醇稳态进行细胞特异性分析将增强我们对神经退行性疾病中胆固醇代谢的理解。操纵胆固醇水平以恢复体内平衡可能代表减轻神经症状的新方法。
背景：一个重大进展是将星形胶质细胞衍生的ApoE鉴定为神经元从头胆固醇生物合成的关键调节剂，提供有关细胞外信号如何影响神经元胆固醇水平的见解。此外,基于抗体的疗法的发展，特别是对于AD,为治疗干预提供了有希望的机会。
结果：尽管进行了大量研究，胆固醇和神经退行性疾病之间的关系仍然没有定论。区分血浆胆固醇和脑胆固醇至关重要，因为这些池相对独立。在评估基于他汀类药物的治疗方法时，应考虑这种差异。不仅要评估大脑中的总胆固醇含量，还要评估其在不同类型脑细胞中的分布。
结论：建立脑/血浆胆固醇水平变化与脑功能障碍/神经退行性疾病发病之间的因果关系仍然是一个关键目标。此外,在病理条件下对各种类型的脑细胞中的胆固醇稳态进行细胞特异性分析将增强我们对神经退行性疾病中胆固醇代谢的理解。操纵胆固醇水平以恢复体内平衡可能代表减轻神经症状的新方法。
