Altered cholesterol and fatty acid metabolism in Huntington disease.
Altered cholesterol and fatty acid metabolism in Huntington disease.
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DOI：
10.1016/j.jacl.2009.11.003
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发表时间：
2010-01
影响因子：
4.4
通讯作者：
Shoulson, Ira
中科院分区：
文献类型：
--
作者：
Block, Robert C.;Dorsey, E. Ray;Beck, Christopher A.;Brenna, J. Thomas;Shoulson, Ira
亨廷顿病是一种常染色体显性遗传的神经退行性疾病，其特征是行为异常、认知下降和不自主运动，导致功能能力、独立性的进行性下降，并最终死亡。亨廷顿病的病理生理学与4号染色体上IT-15基因中胞嘧啶-腺嘌呤-鸟嘌呤（CAG）的扩增三核苷酸重复有关。对于亨廷顿病没有疾病修饰治疗，并且需要新的病理生理学见解和治疗策略。脂质对中枢神经系统的健康至关重要，对动物和人类的研究表明，胆固醇代谢在亨廷顿病中被破坏。这种脂质失调与突变亨廷顿蛋白对固醇调节元件结合蛋白的特异性作用有关。这导致大脑受影响区域的胆固醇水平降低，有证据表明这种消耗是病理性的。亨廷顿病还与胰岛素抗性模式相关，其特征在于分解代谢状态，导致体重减轻和比没有亨廷顿病的个体更低的体重指数。胰岛素抵抗似乎是伴随疾病进展的代谢应激源。鱼中的ω-3脂肪酸，二十碳五烯酸和二十二碳六烯酸，已经在亨廷顿病患者的临床试验中进行了检查。对抗亨廷顿病中脂质环境失调的药物可能有助于治疗这种令人困惑的灾难性遗传疾病。
Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.
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DOI：
10.1016/j.plefa.2009.05.015
发表时间：
2009-08
期刊：
Prostaglandins, leukotrienes, and essential fatty acids
影响因子：
--
作者：
Cole GM;Ma QL;Frautschy SA
通讯作者：
Frautschy SA
影响因子：
6.6
作者：
da Silva, Ticyana Moralez;Munhoz, Renato Puppi;Ferraz, Anete Curte
通讯作者：
Ferraz, Anete Curte
影响因子：
2.8
作者：
Davidson, Michael H.
通讯作者：
Davidson, Michael H.
影响因子：
4.8
作者：
Quintanilla, Rodrigo A.;Jin, Youngnam N.;Johnson, Gail V. W.
通讯作者：
Johnson, Gail V. W.
影响因子：
4.3
作者：
Chen, Stephen T.;Darby, Ivan B.;Clement, John G.
通讯作者：
Clement, John G.