胆固醇可能是阿尔茨海默氏病,糖尿病新疗法的关键

2021-03-26 K.K MedSci原创

胆固醇可能是阿尔茨海默氏病,糖尿病新疗法的关键

目前,阿尔茨海默病尚无治疗方法,该病在美国影响着550多万人。在过去十年中,科学家们发现越来越多的证据表明:2型糖尿病和阿尔茨海默病有关联。

近日,一项发表在ACS Pharmacology & Translational Science杂志上的研究,来自亚利桑那大学健康科学研究人员发现了胆固醇在治疗阿尔茨海默病和2型糖尿病中发挥的作用,并找到了一种有助于调节大脑的胆固醇的小分子,有望成为治疗阿尔茨海默病的潜在靶点。

 

Manel Ben Aissa et al, Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes, ACS Pharmacology & Translational Science (2021). DOI: 10.1021/acsptsci.0c00149

当胰岛素从血液中清除葡萄糖的效率变低时,就会导致高血糖,产生2型糖尿病,从而导致胆固醇水平异常。阿尔茨海默病也会出现类似的情况,但这种影响不是影响整个身体,而是发生在大脑局部。

"阿尔茨海默病和糖尿病有许多共同的发病原因。"亚利桑那药学院药理学和毒理学教授Gregory Thatcher说。

载脂蛋白E (APOE)是一种参与胆固醇逆向转运的蛋白质。它是阿尔茨海默病最典型的风险因素的基因,也是患2型糖尿病和心血管疾病的独立风险因素。当胰岛素抵抗发生而导致胆固醇升高时,人体就会开始一个被称为“反向胆固醇运输”的过程,在此过程中,特定的分子会将多余的胆固醇运送到肝脏并将其排出体外。Thatcher博士说,"将胆固醇移动到身体需要的地方,对许多生理过程都有积极的影响,可以帮助清除积聚在大脑中变形的蛋白质。"

研究人员发现一种胆固醇转运体—ABCA1的活性降低与心血管疾病、2型糖尿病和阿尔茨海默病的风险增加有关。提高ABCA1的活性有望促进胰岛素的分泌、减少大脑中的炎症,可能成为治疗2型糖尿病和阿尔茨海默病的潜在疗法。研究团队设计了一种方法,以确定改善ABCA1的活性,还能避免对肝脏产生不利影响。Thatcher博士的团队对一种特定的小分子化合物CL2-57进行了研究,因为它能刺激ABCA1活性,对肝脏和血浆中的甘油三酯都有积极的影响,使用这种化合物可能改善胰岛素敏感性、减少体重增加等。

他们未来的研究将寻求改善小分子的特性,以提高大脑中的水平。他们的长期目标是了解哪些患有阿尔茨海默氏症和痴呆症的认知和神经精神症状的患者将从治疗中受益。

"在COVID-19大流行期间,我们听到养老院的死亡人数越来越多,重要的是要记住,阿尔茨海默氏症和相关的痴呆症是老年人转移到养老院的主要原因,"撒切尔博士说。"如果能想到一个健康跨度被延长的未来,特别是一个健康的大脑,那将是一件好事,也许这比寿命更重要。"

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    2021-03-28 kcb074
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    2021-03-26 妙酒

    1.低密度脂蛋白 糖尿病 阿尔兹海默症三者密切相关 2.阿尔兹海默类似朊病毒,但是慢性温和不可逆

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    2021-03-26 misszhang

    谢谢MedSci提供最新的资讯

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