The long term effects of uncoupling interventions as a therapy for dementia in humans
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Abstract
In this paper we use simulation methods to study a hypothetical uncoupling agent as a therapy for dementia. We simulate the proliferation of mitochondrial deletion mutants amongst a population of wild-type in human neurons. Mitochondria play a key role in ATP generation. Clonal expansion can lead to the wild-type being overwhelmed by deletions such that a diminished population can no longer fulfil a cell's energy requirement, eventually leading to its demise. The intention of uncoupling is to reduce the formation of deletion mutants by reducing mutation rate. However, a consequence of uncoupling is that the energy production efficacy is also reduced which in turn increases wild-type copy number in order to compensate for the energy deficit. The results of this paper showed that uncoupling reduced the severity of dementia, however, there was some increase in cognitive dysfunction pre-onset of dementia. The effectiveness of uncoupling was dependent upon the timing of intervention relative to the onset of dementia and would necessitate predicting its onset many years in advance. [Abstract copyright: Copyright © 2024 Elsevier Ltd. All rights reserved.]Citation
Holt, A. G., & Davies, A. M. (2024). The long term effects of uncoupling interventions as a therapy for dementia in humans. Journal of Theoretical Biology, 587, article-number 111825. https://doi.org/10.1016/j.jtbi.2024.111825Publisher
ElsevierJournal
Journal of Theoretical BiologyType
ArticleDescription
This article is not available on ChesterRepISSN
0022-5193ae974a485f413a2113503eed53cd6c53
10.1016/j.jtbi.2024.111825