Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease-Parkinson's disease overlap?
Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease-Parkinson's disease overlap?
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DOI：
10.1016/j.exger.2014.09.013
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发表时间：
2015-08
影响因子：
3.9
通讯作者：
Ghribi, Othman
中科院分区：
文献类型：
--
作者：
Marwarha, Gurdeep;Ghribi, Othman
阿尔茨海默病（Alzheimer's disease，AD）是最常见的痴呆形式，其组织病理学特征是脑内β-淀粉样蛋白（Aβ）斑块和神经元缠结的沉积，其中含有过度磷酸化的tau蛋白。帕金森病（Parkinson's disease，PD）是最常见的运动障碍，其特征是α-突触核蛋白在路易体包涵体中聚集，黑质多巴胺能神经元死亡。基于其病理特征，AD和PD可以被认为是两种不同的疾病实体。然而，PD患者亚群也表现出Aβ斑块，AD患者表现出α-突触核蛋白聚集体。PD和AD之间的这种重叠表明这两种疾病存在共同的病理途径。确定这些因素可以触发AD/PD重叠的病理标志的因素和细胞机制可能有助于设计可以逆转或阻止AD和PD进展的疾病修饰疗法。在过去的十年中，我们实验室的工作表明，胆固醇氧化产物（氧化固醇）水平的波动可能与AD和PD的发病相关。在这篇综述中，我们将提供从我们的实验室和文献中的数据，收敛到强烈建议参与的胆固醇和胆固醇氧化产物在AD和PD的发病机制的结果。我们将具体描述的作用和潜在的机制，增加水平的氧化固醇27-羟基胆固醇有助于AD，PD和AD/PD重叠的发病机制。
Alzheimer’s disease (AD), the most common form of dementia, is characterized histopathologically by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles-containing hyperphosphorylated tau protein in the brain. Parkinson’s disease (PD), the most common movement disorder, is characterized by the aggregation of α-synuclein protein in Lewy body inclusions and the death of dopaminergic neurons in the substantia nigra. Based on their pathological signatures, AD and PD can be considered as two different disease entities. However, a subpopulation of PD patients also exhibit Aβ plaques, and AD patients exhibit α-synuclein aggregates. This overlap between PD and AD suggests that common pathological pathways exist for the two diseases. Identification of factors and cellular mechanisms by which these factors can trigger pathological hallmarks for AD/PD overlap may help in designing disease-modifying therapies that can reverse or stop the progression of AD and PD. For the last decade, work in our laboratory has shown that fluctuations in the levels of cholesterol oxidation products (oxysterols) may correlate with the onset of AD and PD. In this review, we will provide results from our laboratory and data from literature that converge to strongly suggest the involvement of cholesterol and cholesterol oxidation products in the pathogenesis of AD and PD. We will specifically delineate the role of and the underlying mechanisms by which increased levels of the oxysterol 27-hydroxycholesterol contribute to the pathogenesis of AD, PD, and AD/PD overlap.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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