Nat Med：一种通路会诱发阿尔茨海默氏症和朊病毒病

2014-01-02 张笑中国科学报

《自然—医学》上的一项研究发现了一种对阿尔茨海默氏症（又称老年痴呆症）和朊病毒疾病发展有促进作用的共同通路。抑制该通路可减缓小鼠体内这两类疾病的发病过程，这意味着开发针对该通路的单一药物可能会对治疗这两类疾病有所帮助。在这两类疾病中，淀粉样前体蛋白和朊蛋白会在细胞表面分别发生分裂。一种名为α-分泌酶分裂的保护性通路会让这些蛋白阻碍在发病过程中积累的有毒蛋白的形成。 Benoit Schnei

《自然—医学》上的一项研究发现了一种对阿尔茨海默氏症（又称老年痴呆症）和朊病毒疾病发展有促进作用的共同通路。抑制该通路可减缓小鼠体内这两类疾病的发病过程，这意味着开发针对该通路的单一药物可能会对治疗这两类疾病有所帮助。

在这两类疾病中，淀粉样前体蛋白和朊蛋白会在细胞表面分别发生分裂。一种名为α-分泌酶分裂的保护性通路会让这些蛋白阻碍在发病过程中积累的有毒蛋白的形成。

Benoit Schneider、Jean-Marie Launay等人报告称α-分泌酶的活性会随着小鼠感染朊病毒而降低，或者发生基因变异促使阿尔茨海默氏症类疾病的发生。而这种情况与阿尔茨海默氏症患者大脑内的激酶PDK1的活性增加有关，此外，患这些疾病的小鼠体内也存在有这种关联性。从药理学或基因学方面实现对小鼠体内PDK1的抑制可以保护神经元不受朊病毒和β-淀粉样的毒性影响，并可以促进α-分泌酶的保护性通路。

在感染朊病毒的小鼠体内，抑制PDK1可以延迟疾病发作，延长存活率并降低运动功能障碍的发生。同样的抑制剂在作用于三类不同的经过转基因改造的阿尔茨海默氏症患病小鼠身上后，也会降低阿尔茨海默氏症类病理性症状以及记忆功能障碍的发生。

原文出处

Pietri M, Dakowski C, Hannaoui S, Alleaume-Butaux A, Hernandez-Rapp J, Ragagnin A, Mouillet-Richard S, Haik S, Bailly Y, Peyrin JM, Launay JM, Kellermann O, Schneider B.PDK1 decreases TACE-mediated α-secretase activity and promotes disease progression in prion and Alzheimer's diseases.Nat Med. 2013 Sep

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2022-03-19 医者仁者

#朊病毒#，#克雅氏病#

0 0
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2014-11-21 ms1948154235210413

#阿尔茨#

24 0
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2014-01-30 12498da4m32(暂无昵称)

#阿尔茨海#

43 0
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2014-12-13 liye789132251

#Nat#

28 0
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2014-06-06 zhs3882

#阿尔茨海默氏#

0 0
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2014-01-04 yhj-time

#阿尔茨海默#

29 0
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2014-01-04 ms3994565386320060

#Med#

25 0

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