Science Journal: inhibition of msut2 may protect brain from damage caused by abnormal accumulation of tau protein

December 28, 2019 / Biovalley BIOON / - -- after the recent failure of clinical trials targeting β - amyloid (a β) plaque accumulation in Alzheimer's disease, people pay more attention to the misfolded tau protein, in which tau is another culprit of brain diseases leading to dementia Like a β, tau accumulates in Alzheimer's disease and causes brain cell damage However, the number of clinical trials targeting tau is much smaller, which is partly due to the difficulty in finding drugs targeting tau In a new study, researchers from the University of Washington School of medicine and the Department of Veterans Affairs's Puget Bay health system found hope by targeting abnormal tau egg whites by suppressing a gene called msut2 They concluded that as long as an RNA binding protein called PABPN1 (Polya binding protein nuclear 1) is not depleted, inhibiting msut2 may protect people from Alzheimer's disease Msut2 and pabpni usually work closely together to regulate the biological characteristics of tau in the brain The related research results were recently published in the Journal of Science Translational Medicine The title of the paper is "activity of the poly (a) binding protein msut2 determinations sustainability to pathway tau in the mamman brain" Tau protein tangle in mouse brain, picture from UW medicine "If we can inhibit msut2 without affecting pabn1, then we can prevent the influence of tau pathology," said Brian Kraemer, the corresponding author of the paper and associate professor of medical research at the University of Washington School of medicine "Pharmaceutical companies have invested a lot in research and development of a β, but so far, these efforts have not promoted the development of dementia treatment," he said I think this area needs to consider targeting both a β and tau, because a β and tau proteins work together to kill neurons in Alzheimer's disease " Jeanna Wheeler, CO lead author of the paper and a researcher at the Seattle Institute of biomedical and clinical research, Puget Bay health system, Department of Veterans Affairs, said the novelty of the study was the discovery of the role of the msut2 gene "We first discovered msut2 in a completely unbiased way by looking for substances that make nematodes resistant to pathological tau proteins," she said Now, we have confirmed that this gene can also affect tau toxicity in mice, and there are differences in msut2 in human Alzheimer's patients If we can use msut2 as a drug target in the future, it will be a new way to treat Alzheimer's disease and other related diseases " This new study also makes people pay more attention to the role of tau pathological characteristics in Alzheimer's disease The healthy human brain contains tens of billions of neurons that can process and transmit information By destroying the communication between these neurons, Alzheimer's disease can lead to the loss of neuron function and cell death Previous studies have shown that the abnormal accumulation of tau in patients with Alzheimer's disease is closely related to the decline of cognitive ability, but a β is not Some dementia, such as frontotemporal degeneration, may have only abnormal tau deposition but no a β deposition Kraemer said, "if we can protect the brain from TAU alone, it may bring great benefits to Alzheimer's patients Similarly, tau targeting Alzheimer's disease-related tangled dementia, such as frontotemporal degeneration, is almost certainly beneficial to patients " The study was based on a previous study by the researchers, which used C elegans to produce very similar results The nematode will change from egg to adult within three days, which makes it easier to conduct rapid aging experiments in biology Although nematodes have no complex cognitive function, their activities are affected by tau accumulation They found that they could cure nematodes by knocking out the sut-2 gene The new study takes this experiment in mice, which are much closer to humans than nematodes The researchers knocked out the msut2 gene in mice, thus preventing the formation of tau tangles that kill brain cells It also reduces learning and memory problems When the researchers studied brain samples from autopsies of Alzheimer's patients, they found that patients with more severe conditions lacked both msut2 and its chaperone, PABPN1 This finding suggests that neurons that lose the msut2-pabpn1 protein partnership may die in a patient's lifetime In addition, mice lacking msut2 but with normal PABPN1 were strongly resistant to abnormal tau accumulation and brain degeneration Therefore, the researchers concluded that the key to help people with abnormal accumulation of tau is to block msut2 while retaining the activity of PABPN1 (bio Com) reference: 1 Jeanna M Wheeler et al Activity of the poly (a) binding protein msut2 determinations applicability to pathway tau in the mammary brain Science Translational Medicine, 2019, doi:10.1126/scitranslmed.aao6545 2.Alzheimer's study shows promise in protecting brain from tau https://medicalxpress.com/news/2019-12-alzheimer-brain-tau.html