| Autor: |
Peers, Chris, Scragg, Jason L, Boyle, John P, Fearon, Ian M, Taylor, Shafeena C, Green, Kim N, Webster, Nicola J, Ramsden, Martin, Pearson, Hugh A |
| Zdroj: |
Philosophical Transactions B: Biological Sciences; December 2005, Vol. 360 Issue: 1464 p2247-2254, 8p |
| Abstrakt: |
Periods of prolonged hypoxia are associated clinically with an increased incidence of dementia, the most common form of which is Alzheimer's disease. Here, we review recent studies aimed at providing a cellular basis for this association. Hypoxia promoted an enhanced secretory response of excitable cells via formation of a novel Ca2influx pathway associated with the formation of amyloid peptides of Alzheimer's disease. More strikingly, hypoxia potentiated Ca2influx specifically through L-type Ca2channels in three distinct cellular systems. This effect was post-transcriptional, and evidence suggests it occurred via increased formation of amyloid peptides which alter Ca2channel trafficking via a mechanism involving increased production of reactive oxygen species by mitochondria. This action of hypoxia is likely to contribute to dysregulation of Ca2homeostasis, which has been proposed as a mechanism of cell death in Alzheimer's disease. We suggest, therefore, that our data provide a cellular basis to account for the known increased incidence of Alzheimer's disease in patients who have suffered prolonged hypoxic episodes. |
| Databáze: |
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