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- W4312195155 abstract "Chronic hypoxia is a risk factor for Alzheimer's disease (AD), and the neurofibrillary tangle (NFT) formed by hyperphosphorylated tau is one of the two major pathological changes in AD. However, the effect of chronic hypoxia on tau phosphorylation and its mechanism remains unclear. In this study, we investigated the role of HIF-1α (the functional subunit of hypoxia-inducible factor 1) in tau pathology. It was found that in Sprague-Dawley (SD) rats, global hypoxia (10% O2, 6 h per day) for one month induced cognitive impairments. Meanwhile it induced HIF-1α increase, tau hyperphosphorylation, and protein phosphatase 2A (PP2A) deficiency with leucine carboxyl methyltransferase 1(LCMT1, increasing PP2A activity) decrease in the rats' hippocampus. The results were replicated by hypoxic treatment in primary hippocampal neurons and C6/tau cells (rat C6 glioma cells stably expressing human full-length tau441). Conversely, HIF-1α silencing impeded the changes induced by hypoxia, both in primary neurons and SD rats. The result of dual luciferase assay proved that HIF-1α acted as a transcription factor of LCMT1. Unexpectedly, HIF-1α decreased the protein level of LCMT1. Further study uncovered that both overexpression of HIF-1α and hypoxia treatment resulted in a sizable degradation of LCMT1 via the autophagy--lysosomal pathway. Together, our data strongly indicated that chronic hypoxia upregulates HIF-1α, which obviously accelerated LCMT1 degradation, thus counteracting its transcriptional expression. The increase in HIF-1α decreases PP2A activity, finally resulting in tau hyperphosphorylation and cognitive dysfunction. Lowering HIF-1α in chronic hypoxia conditions may be useful in AD prevention." @default.
- W4312195155 created "2023-01-04" @default.
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- W4312195155 date "2022-12-17" @default.
- W4312195155 modified "2023-10-16" @default.
- W4312195155 title "HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia" @default.
- W4312195155 cites W1607924132 @default.
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- W4312195155 cites W1908612571 @default.
- W4312195155 cites W1954244449 @default.
- W4312195155 cites W1966657660 @default.
- W4312195155 cites W1968030855 @default.
- W4312195155 cites W1969872085 @default.
- W4312195155 cites W1971030649 @default.
- W4312195155 cites W1974679183 @default.
- W4312195155 cites W1978071550 @default.
- W4312195155 cites W1985584416 @default.
- W4312195155 cites W1988332799 @default.
- W4312195155 cites W2008657247 @default.
- W4312195155 cites W2009784030 @default.
- W4312195155 cites W2011829284 @default.
- W4312195155 cites W2014235909 @default.
- W4312195155 cites W2016510291 @default.
- W4312195155 cites W2017646265 @default.
- W4312195155 cites W2025500109 @default.
- W4312195155 cites W2029612152 @default.
- W4312195155 cites W2030333049 @default.
- W4312195155 cites W2031418848 @default.
- W4312195155 cites W2036011584 @default.
- W4312195155 cites W2053276094 @default.
- W4312195155 cites W2056820600 @default.
- W4312195155 cites W2060499103 @default.
- W4312195155 cites W2073012903 @default.
- W4312195155 cites W2080374319 @default.
- W4312195155 cites W2081458774 @default.
- W4312195155 cites W2083511611 @default.
- W4312195155 cites W2102178368 @default.
- W4312195155 cites W2110495164 @default.
- W4312195155 cites W2111200377 @default.
- W4312195155 cites W2120090919 @default.
- W4312195155 cites W2129085204 @default.
- W4312195155 cites W2139628971 @default.
- W4312195155 cites W2166435019 @default.
- W4312195155 cites W2172968584 @default.
- W4312195155 cites W2257069691 @default.
- W4312195155 cites W2600000174 @default.
- W4312195155 cites W2612500343 @default.
- W4312195155 cites W2623778730 @default.
- W4312195155 cites W2744402516 @default.
- W4312195155 cites W2749492625 @default.
- W4312195155 cites W2753434084 @default.
- W4312195155 cites W2761011647 @default.
- W4312195155 cites W2767311859 @default.
- W4312195155 cites W2808028315 @default.
- W4312195155 cites W2884578044 @default.
- W4312195155 cites W2887518054 @default.
- W4312195155 cites W2890865075 @default.
- W4312195155 cites W2902385652 @default.
- W4312195155 cites W2909203784 @default.
- W4312195155 cites W2920204040 @default.
- W4312195155 cites W2958665365 @default.
- W4312195155 cites W3012822407 @default.
- W4312195155 cites W3018379887 @default.
- W4312195155 cites W3022931636 @default.
- W4312195155 cites W3042981350 @default.
- W4312195155 cites W3048109944 @default.
- W4312195155 cites W3048534009 @default.
- W4312195155 cites W3125450900 @default.
- W4312195155 cites W3130977957 @default.
- W4312195155 cites W3138163199 @default.
- W4312195155 cites W3138760932 @default.
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- W4312195155 doi "https://doi.org/10.3390/ijms232416140" @default.
- W4312195155 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36555780" @default.
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