Cell sub-journal interpretation! Uncover the molecular processes of hypoxia that damage brain health!

26, 2020 /PRNewswire/ -- In a recent study published in the international journal Cell Stem Cell entitled "Non-canonical Targets of HIF1a Impaired Oligodendrocyte Progenitor Cell Function", scientists from kessie storage university school of medicine and others found that abnormal brain cell function in hypoxia may have been triggered by the same response system that was originally protective.
researcher Professor Paul Tesar said these powerful protein responders initially protected brain cells from hypoxia, but we found that their long-term activation may have caused some unexpected damage that ultimately impaired brain cell function.
Clarifying the mechanisms of brain cell damage in hypoxia may provide researchers with the opportunity to develop new and effective therapies, including a class of drugs currently being studied by researchers that promise to help treat neurological disorders induced by low oxygen levels in clinical practice, and the results of this paper can also help clarify how the body's response to low oxygen levels induces disease in tissues other than the brain.
With the ad emergence of an oxygenated atmosphere, the emergence of multicellular life became possible because oxygen could be used to produce the energy needed to support the functional maintenance of multicellular life; given the need for oxygen, almost all organisms could evolve a mechanism to react quickly to hypoxia , and the 2019 Nobel Prize in Medicine or Physiology was awarded to studies that shed light on how the body perceives and reacts to it.
Photo Source: Case Western Reserve University Researchers point out that the core of this ancient reaction is a protein called hypoxia-inducing factor (HIFs), which is thought to protect and resuscitated cells in low-oxygen conditions by directing cells to minimize oxygen consumption and maximize oxygen.
Long-term hypoxia can cause abnormalities in many tissues, especially stem cells in the brain, which can be impaired by hypoxia in a variety of diseases, including stroke, prema premature-related cerebral palsy, respiratory distress syndrome, multiple sclerosis and vascular dementia, and even major neurological damage caused by COVID-19.
So far, researchers don't know the exact molecular causes behind cellular abnormalities induced by hypoxia; in this study, researchers developed a new way to analyze the molecular mechanisms by which hypoxia-reactive proteins function by comparing their functional differences in brain stem cells and other tissues, such as heart tissue and skin tissue. It has been confirmed that in hypoxia, hypoxia-reactive proteins can perform beneficial functions in all tissues to promote cell survival, but the same hypoxia-reactive protein may also have a dark side that has not been previously noted, that is, it can open up other cellular processes in addition to the beneficial reactions that can open the core.
Then the researchers discovered an additional reaction that could impair the function of stem cells in the brain, which was not previously known to the researchers, suggesting that hypoxia-reactive proteins may have evolved to promote cell survival in all tissues of the body in oxygen-deprived conditions, but this powerful effect can also have abnormal consequences such as interfering with cell function.
Then the researchers tested thousands of drugs to try to restore stem cell function in the brain while overcoming the damaging effects of hypoxia-reactive proteins, and found that a particular class of drugs could specifically overcome this damage-induced response while keeping the original beneficial response intact.
Kevin Allan, lead author of the final article, said: 'What's very exciting about this study is that we've identified a particular drug that specifically targets the effects of hypoxia-reactive damage while also releasing beneficial effects, which may provide new research perspectives and ideas for later scientists to fight all tissue damage from hypoxia.'
Whether the destructive side of the hypoxia response is more than just an unexpected pathological effect, or perhaps a previously undiscovered normal process (a problem occurs during the course of a disease), is still unknown; this study provides new ideas and research for later scientists to develop new ways to understand how cells respond to hypoxia during the course of the body's health and disease.
() References: Kevin C. Allan, Lucille R. Hu, Marissa A. Scavuzzo, et al. Non-canonical Targets of HIF1a Impaired Oligodendrocyte Progenitor Cell Function, Cell Stem Cell (2020) doi:10.1016/j.stem.2020.09.019 (2) New Research Reveals Why low oxygens the brainby Case Western Reserve University.