1. Dysregulated Wnt Signalling in the Alzheimer’s Brain
- Author
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Hanqing Jin, Nozie D. Aghaizu, and Paul Whiting
- Subjects
APP processing ,tau pathology ,Central nervous system ,blood brain barrier ,Review ,Blood–brain barrier ,lcsh:RC321-571 ,neuroinflammation ,Synapse ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Amyloid precursor protein ,Dementia ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroinflammation ,Wnt signalling ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,General Neuroscience ,Neurodegeneration ,Neurogenesis ,neurodegeneration ,synapse degeneration ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,business ,Neuroscience ,Alzheimer’s disease ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2020