Projects per year
Abstract
Willin/FRMD6 has been reported as a potential Alzheimer’s disease risk gene in a series of genome-wide association and neuroimaging studies; however, the mechanisms underlying its potential role in AD pathogenesis remain unknown. Here, we demonstrate the direct effects of Aβ on Willin/FRMD6 expression and position mitochondrial oxidative stress as a novel potential mechanism underlying the role of Willin/FRMD6 in AD pathogenesis. Specifically, using mouse hippocampal HT-22 cells and primary mouse neurons, we show that Aβ induces downregulation of the Willin/FRMD6 protein. Furthermore, we demonstrate that Willin/FRMD6 knockdown leads to mitochondrial dysfunction and fragmentation, as well as upregulation of ERK1/2 signaling, both of which are reported to be key early features of AD pathogenesis. Importantly, increasing Willin/FRMD6 expression was able to rescue Aβ-induced abnormalities in mitochondrial morphology, function, and energetics. Thus, enhancing Willin/FRMD6 expression holds potential as a therapeutic strategy for protecting against Aβ-induced mitochondrial and neuronal dysfunction.
Original language | English |
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Article number | 3140 |
Number of pages | 27 |
Journal | Cells |
Volume | 11 |
Issue number | 19 |
DOIs | |
Publication status | Published - 6 Oct 2022 |
Keywords
- Willin/FRMD6
- Mitochondiral dysfunction
- Oxidative stress
- Alzheimer's disease
- Neurodegeneration
- ERK signaling
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- 1 Finished
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Resonant and shaped photonics for under: Resonant and shaped photonics for understanding the physical and biomedical world
Gunn-Moore, F. J. (PI)
1/08/17 → 31/07/22
Project: Standard