Petrov A M, Kasimov M R, Zefirov A L
Kazan State Medical University, Normal Physiology department, Butlerova str. 49, Kazan, 420012, Russia.
Acta Naturae. 2017 Jan-Mar;9(1):26-37.
In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production. Notably, alterations in the brain cholesterol metabolism and neurotransmission occur in the early stages of these pathologies and the polymorphism of the genes associated with cholesterol homeostasis and synaptic communication affects the risk of onset and severity of these diseases. In addition, pharmacological and genetic manipulations of brain cholesterol homeostasis in animal models frequently have marked effects on the progression of neurodegenerative diseases. Thus, the development of Alzheimer's, Parkinson's and autism spectrum disorders may be partially associated with an imbalance of cholesterol homeostasis that leads to changes in the membrane cholesterol and oxysterol levels that, in turn, modulates key steps in the synaptic transmission.
在我们之前的综述中，我们描述了在对照条件下以及在一些与直接参与胆固醇合成和/或运输的基因缺陷相关的罕见神经病理学情况下的脑胆固醇代谢。在此，我们分析了广泛的神经退行性疾病（阿尔茨海默病和帕金森病）以及自闭症谱系障碍中胆固醇稳态的破坏情况。我们特别关注了可能因膜胆固醇可用性和氧化甾醇产生的变化而出现的突触功能障碍。值得注意的是，这些疾病的早期阶段会出现脑胆固醇代谢和神经传递的改变，并且与胆固醇稳态和突触通讯相关的基因多态性会影响这些疾病的发病风险和严重程度。此外，动物模型中脑胆固醇稳态的药理学和基因操作常常对神经退行性疾病的进展有显著影响。因此，阿尔茨海默病、帕金森病和自闭症谱系障碍的发展可能部分与胆固醇稳态失衡有关，这种失衡会导致膜胆固醇和氧化甾醇水平的变化，进而调节突触传递中的关键步骤。
