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首页> 外文期刊>Neuron >Loss of A beta 43 Production Caused by Presenilin-1 Mutations in the Knockin Mouse Brain
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Loss of A beta 43 Production Caused by Presenilin-1 Mutations in the Knockin Mouse Brain

机译:在敲小鼠脑中由早老素-1突变引起的A beta 43生产的损失。

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We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer's disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1(-/-) mice. Production and steady-state levels of A beta 40 and A beta 42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the A beta 42/A beta 40 ratio is slightly increased in KI/+ brains. Moreover, the FAD mutation impairs synaptic function, learning and memory, and age-dependent neuronal survival in the adult brain. Here we extend our analysis of the effects of the L435F and C410Y mutations to the generation of A beta 43. Similar to A beta 40 and A beta 42, production of A beta 43 is undetectable in KI/KI brains and reduced in KI/+ brains. These results support our previous conclusions that the L435F and C410Y mutations cause loss of Presenilin function and gamma-secretase activity, including impaired A beta production in the brain. This Matters Arising Response paper addresses the Veugelen et al. (2016) Matters Arising paper, published concurrently in Neuron.
机译:我们最近报道,携带家族性阿尔茨海默氏病(FAD)突变L435F或C410Y的纯合子Presenilin-1(Psen1)敲入(KI)小鼠概括了Psen1(-/-)小鼠的表型。尽管KI / +大脑中的A beta 42 / A beta 40比例略有增加,但在KI / KI大脑中无法检测到A beta 40和A beta 42的产生水平和稳态水平,而在KI / +大脑中则有所降低。此外,FAD突变会损害成人大脑中的突触功能,学习和记忆以及年龄依赖性神经元存活。在这里,我们将对L435F和C410Y突变的影响的分析扩展到A beta 43的产生。类似于A beta 40和A beta 42,在KI / KI脑中无法检测到A beta 43的产生,并且在KI / +中减少大脑。这些结果支持了我们先前的结论,即L435F和C410Y突变会导致早老素功能和γ-分泌酶活性的丧失,包括大脑中Aβ的产生受损。此问题引起的回应论文针对Veugelen等人。 (2016)Matters Arising论文,同时发表在Neuron上。

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