Proteolytic cleavage of apolipoprotein E4 as the keystone for the heightened risk associated with Alzheimer's disease.
Proteolytic cleavage of apolipoprotein E4 as the keystone for the heightened risk associated with Alzheimer's disease.
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DOI：
10.3390/ijms140714908
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发表时间：
2013-07-17
影响因子：
5.6
通讯作者：
Rohn TT
中科院分区：
文献类型：
--
作者：
Rohn TT
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征在于由β-淀粉样蛋白斑块和神经纤维缠结（NFT）组成的显微病变。大多数病例被定义为散发性的，可能是由遗传和环境因素共同引起的。在确定的遗传风险因素中，34 kDa蛋白质载脂蛋白（apo）E4具有重要意义，因为APOE 4携带者占所有AD病例的65%-80%。虽然apoE 4在脂蛋白转运中起着正常的作用，但它如何参与AD的发病机制目前尚不清楚。apoE 4导致疾病风险的一个潜在机制是其倾向于经历蛋白水解切割产生N-和C-末端片段。本综述的目的将是检查的机制，载脂蛋白E4有助于AD的发病机制，重点是潜在的损失或获得的功能，可能会发生以下全长蛋白裂解。在这种情况下，是否靶向apoE 4治疗是一个合理的方法来治疗这种疾病的讨论将进行评估。
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by microscopic lesions consisting of beta-amyloid plaques and neurofibrillary tangles (NFTs). The majority of cases are defined as sporadic and are likely caused by a combination of both genetic and environmental factors. Of the genetic risk factors identified, the 34 kDa protein, apolipoprotein (apo) E4, is of significant importance as APOE4 carriers account for 65%–80% of all AD cases. Although apoE4 plays a normal role in lipoprotein transport, how it contributes to AD pathogenesis is currently unknown. One potential mechanism by which apoE4 contributes to disease risk is its propensity to undergo proteolytic cleavage generating N- and C-terminal fragments. The purpose of this review will be to examine the mechanisms by which apoE4 contributes to AD pathogenesis focusing on the potential loss or gain of function that may occur following cleavage of the full-length protein. In this context, a discussion of whether targeting apoE4 therapeutically is a rationale approach to treating this disease will be assessed.
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DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
4.8
作者：
Chen, Hung-Kai;Ji, Zhong-Sheng;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
影响因子：
4.8
作者：
Chen, Hung-Kai;Liu, Zhaoping;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
16.2
作者：
BRAMBLETT, GT;GOEDERT, M;LEE, VMY
通讯作者：
LEE, VMY