Dysregulated Wnt Signalling in the Alzheimer's Brain.

Dysregulated Wnt Signalling in the Alzheimer's Brain.
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DOI:
10.3390/brainsci10120902
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发表时间:
2020-11-24
期刊:
影响因子:
3.3
通讯作者:
Whiting PJ
Whiting PJ
中科院分区:
医学4区
文献类型:
--
作者:
Aghaizu ND;Jin H;Whiting PJ

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Wnt信号系统对于发育和成年中枢神经系统都是必不可少的。它调节从神经发生到血脑屏障生物学的许多细胞功能。因此,Wnt信号转导失调可能对正常的脑功能产生重大影响,这在阿尔茨海默病(AD)中变得越来越明显,阿尔茨海默病是一种与年龄相关的神经退行性疾病,是最常见的痴呆形式。AD表现出一系列病理生理学表现,包括异常淀粉样前体蛋白加工、tau病理学、突触丧失、神经炎症和血脑屏障破坏,这些表现或多或少地与异常Wnt信号传导相关。在这里,我们提供了一个全面的概述Wnt信号在中枢神经系统中的作用,以及研究表明,Wnt信号失调的大脑老化和AD的发病机制。我们还讨论了通过调节Wnt信号通路对AD进行治疗干预的机会,并强调了我们目前理解中需要满足的一些挑战和差距,以实现这一目标。
The Wnt signalling system is essential for both the developing and adult central nervous system. It regulates numerous cellular functions ranging from neurogenesis to blood brain barrier biology. Dysregulated Wnt signalling can thus have significant consequences for normal brain function, which is becoming increasingly clear in Alzheimer’s disease (AD), an age-related neurodegenerative disorder that is the most prevalent form of dementia. AD exhibits a range of pathophysiological manifestations including aberrant amyloid precursor protein processing, tau pathology, synapse loss, neuroinflammation and blood brain barrier breakdown, which have been associated to a greater or lesser degree with abnormal Wnt signalling. Here we provide a comprehensive overview of the role of Wnt signalling in the CNS, and the research that implicates dysregulated Wnt signalling in the ageing brain and in AD pathogenesis. We also discuss the opportunities for therapeutic intervention in AD via modulation of the Wnt signalling pathway, and highlight some of the challenges and the gaps in our current understanding that need to be met to enable that goal.
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