big reversal! the "murderer" of alzheimer's disease actually protects the brain and can effectively remove toxic molecules
2024-09-08
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rightalzheimer's diseasefor ad, there are two classic pathological features, one of which is the excessive accumulation of β-amyloid plaques in the patient's brain, and the other is the neural tangles caused by tau protein. for this reason, tau protein is often identified as the "murderer" that drives the development of ad.on the other hand, tau protein itself is essential for neuronal function. for example, neurons rely heavily on the microtubule system to transport important molecules.tau protein happens to play a role in stabilizing microtubuleshowever, when tau protein is abnormally phosphorylated, aggregates and forms tangles, neurons are unable to remove this “junk” protein, and bad things happen.but this is not the whole story of tau protein. professor hugo belle from baylor college of medicine has long been committed to the study of the brain's nervous system. in a recent study published in nature neuroscience, he and his colleagues jointly proved thattau protein not only maintains the normal work of microtubules, but is also a key component in preventing the occurrence of ad. tau protein can effectively help glial cells remove toxic lipids and reduce damage to neurons.when various cells perform their functions, they producereactive oxygen species (ros), excessive ros will induce oxidative stress and the production of various toxic molecules, such as lipid peroxides. as an extremely active nervous system, neural tissue not only produces a large amount of ros,neurons are also particularly sensitive to high levels of ros., so the brain also has various strategies to deal with the effects of ros.professor belle once discovered that when neurons are faced with ros, they will transport the produced lipid peroxidation to glial cells, which will accumulate these lipids and isolate them from the surrounding environment in the form of lipid droplets. later, they can even digest and decompose these lipids for energy supply, achieving the effect of killing two birds with one stone.other studies have found that when tau protein is overexpressed in neuronal or glial cell models, high levels of ros can be observed. conversely, when ros increases, tau protein expression in zebrafish can also be upregulated. so what are the specific balance mechanisms between tau protein and ros?in the new study, the authors first tried to overexpress tau protein in the retina of fruit flies. glial cells in this area are also affected by ros and form lipid droplets. however, when tau protein gradually accumulates uncontrollably,the morphology of glial cells changed, making them more sensitive to ros and their ability to form lipid droplets was significantly weakened.in addition, excessive accumulation of tau protein in the fruit fly brain also interferes with the ability of glial cells to form lipid droplets. this is actually not particularly unexpected.▲if the level of tau protein is too high, the lipid droplet formation ability of glial cells will be impaired(image source: reference [1])
the authors then did the opposite and created fruit flies that lacked tau protein. however, these fruit flies did not perform any better, as their glial cells were unable to collect lipid peroxides and form lipid droplets normally. at the same time, the fruit flies showed neurodegenerative changes, especially obvious motor deficits.the reason for this is thattau protein is essential for glial lipid droplet formation, it can not only regulate lipid metabolism, but also help glial cells better cope with ros. this also shows that tau protein has a new neuroprotective effect. at the same time, tau protein needs to be maintained at a reasonable level. too much or too little will lose its protective effect.professor belle pointed out that tau protein is often considered to play the role of "bad guy" in neurodegenerative diseases, but the new research shows that at least they are definitely "good guys" in glial cells. these results will also make us re-understand the role of tau protein in healthy brain and neurological diseases.alzheimer's disease (ad) is one of the major medical problems facing humanity. by 2050, the number of alzheimer's patients worldwide may triple from now.why is alzheimer's disease so difficult to treat?how much do we know about the causes of alzheimer's disease?what new treatments for alzheimer’s disease are worth paying attention to recently?what can we do in our lives to avoid getting sick?
