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载脂蛋白E基因多态性在大脑从出生到老年正常及病理状态下的影响。

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan.

作者信息

Iacono Diego, Feltis Gloria C

机构信息

Neuropathology Research, Biomedical Research Institute of New Jersey (BRInj), Cedar Knolls, NJ 07927, USA.

MidAtlantic Neonatology Associates (MANA), Morristown, NJ 07960, USA.

出版信息

Aging (Albany NY). 2019 Jan 24;11(2):787-816. doi: 10.18632/aging.101757.

Abstract

The central nervous system (CNS) is the cellular substrate for the integration of complex, dynamic, constant, and simultaneous interactions among endogenous and exogenous stimuli across the entire human lifespan. Numerous studies on aging-related brain diseases show that some genes identified as risk factors for some of the most common neurodegenerative diseases - such as the allele 4 of gene () for Alzheimer's disease (AD) - have a much earlier neuro-anatomical and neuro-physiological impact. The impact of polymorphism appears in fact to start as early as youth and early-adult life. Intriguingly, though, those same genes associated with aging-related brain diseases seem to influence different aspects of the brain functioning much earlier actually, that is, even from the neonatal periods and earlier. The , an allele classically associated with later-life neurodegenerative disorders as AD, seems in fact to exert a series of very early effects on phenomena of neuroplasticity and synaptogenesis that begin from the earliest periods of life such as the fetal ones.We reviewed some of the findings supporting the hypothesis that polymorphism is an early modifier of various neurobiological aspects across the entire human lifespan - from the in-utero to the centenarian life - during both normal and pathological conditions of the brain.

摘要

中枢神经系统(CNS)是在整个人类生命周期内整合内源性和外源性刺激之间复杂、动态、持续且同时发生的相互作用的细胞基础。众多关于衰老相关脑部疾病的研究表明,一些被确定为某些最常见神经退行性疾病风险因素的基因——如阿尔茨海默病(AD)的基因()的4号等位基因——具有更早的神经解剖学和神经生理学影响。事实上,多态性的影响早在青年和成年早期就开始显现。然而,有趣的是,那些与衰老相关脑部疾病相关的相同基因似乎实际上更早地影响大脑功能的不同方面,也就是说,甚至从新生儿期及更早开始。经典地与AD等晚年神经退行性疾病相关的等位基因,似乎实际上对从生命最早时期(如胎儿期)开始的神经可塑性和突触发生现象产生一系列非常早期的影响。我们回顾了一些支持以下假设的研究结果:在大脑的正常和病理状态下,多态性是整个人类生命周期(从子宫内到百岁老人阶段)各种神经生物学方面的早期调节因子。

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