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首页> 外文期刊>Nature >Destabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis
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Destabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis

机译：早老素-1突变引起的β-catenin失稳增强神经元凋亡

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Mutations of the presenilin-1 gene are a major cause of familial early-onset Alzheimer's disease. Presenilin-1 can associate with members of the catenin family of signalling proteins, but the significance of this association is unknown. Here we show that presenilin-1 forms a complex with β-catenin in vivo that increases β-catenin stability. Pathogenic mutations in the presenilin-1 gene reduce the ability of presenilin-1 to stabilize β-catenin, and lead to increased degradation of β-catenin in the brains of transgenic mice. Moreover, β-catenin levels are markedly reduced in the brains of Alzheimer's disease patients with presenilin-1 mutations. Loss of β-catenin signalling increases neuronal vulnerability to apoptosis induced by amyloid-β protein. Thus, mutations in presenilin-1 may increase neuronal apoptosis by altering the stability of β-catenin, predisposing individuals to early-onset Alzheimer's disease.
机译：presenilin-1基因的突变是家族性早发性阿尔茨海默氏病的主要原因。 Presenilin-1可以与信号蛋白catenin家族的成员相关联，但这种关联的意义尚不清楚。在这里，我们显示presenilin-1在体内与β-catenin形成复合物，从而增加β-catenin的稳定性。 presenilin-1基因的致病性突变会降低presenilin-1稳定β-catenin的能力，并导致转基因小鼠大脑中β-catenin的降解增加。此外，β-连环蛋白水平在早老素-1突变的阿尔茨海默氏病患者的大脑中显着降低。 β-catenin信号的缺失增加了神经元对淀粉样β-蛋白诱导的凋亡的脆弱性。因此，早老素-1中的突变可通过改变β-catenin的稳定性来增加神经元凋亡，使个体更易患早发性阿尔茨海默氏病。

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