Posted on Jun 29, 2018, 9 p.m.
Tau is widely believed to stabilize microtubules in neurons of the brain, according to a new study tau lengthens microtubes and keeps them dynamic doing the opposite of what was thought, as published in Current Biology.
Drexel University researchers have conducted a study with results reversing popular dogma of tau proteins stabilizing microtubules within brain cells, that its role in neurons is to allow microtubes to grow and remain dynamic. This is a significant finding as stable and dynamic regions of the microtubule must be present for successful cognitive function. Discovery suggests microtubule stabilizing drugs in clinical trials may not be effective in treating tau based neurodegenerative disease such as Alzheimer’s disease.
Popular theory suggests neurodegenerative disease cause patients to lose microtubes because they become less stable; this study suggests with tau depletion patients are losing dynamic regions of microtubules, and treating these disease with microtubule stabilizing drugs causes potential for making things worse.
Infrastructure of a cell is made up of tubular polymers microtubules acting as pathways to transport organelles throughout cytoplasm, that have stable regions and a dynamic region which are both important to their roles within the cell. Tau is a hallmark protein of Alzheimer’s disease that breaks away from microtubules and forms neurofibrillary tangles blocking nutrient transport to neurons which eventually kills them.
Documentation in literally hundreds of research papers, books, websites and other instructional materials support the nearly universally accepted theory that tau’s role is to stabilize microtubules in brain neurons, especially axons nerve fibers. Research groups reported finding that this theory may not be completely correct 20 years ago which lead researchers to delve deeper into the question and further investigate by depleting tau from cultured rat neurons and comparing microtubule levels in axons for four days.
Volumes of microtubules were found to be reduce in the axon, not due to destabilization rather due to preferential loss of dynamic regions of microtubules; depleting tau was observed to make remaining microtubules more stable instead of less altering basic understandings of tau. Rathering than thinking of tau as connection ties needed for stabilization it acts more like a flexible band allowing microtubules to remain constantly in motion so connections don’t crack.
MAP6 was also investigated earning the name genuine stabilizer of microtubules which was found to spread out on microtubules when tau is depleted, which may explain why microtubules become more stable with tau loss.
Further studies will be conducted repeating similar experiments in adult rodent brains, should results be replicated researchers will observe restoration of what was lost in neurodegenerative brains by recovering lost dynamic regions of microtubules via novel therapeutic approaches.
Materials provided by Drexel University.
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Liang Qiang, Xiaohuan Sun, Timothy O. Austin, Hemalatha Muralidharan, Daphney C. Jean, Mei Liu, Wenqian Yu, Peter W. Baas. Tau Does Not Stabilize Axonal Microtubules but Rather Enables Them to Have Long Labile Domains. Current Biology, 2018; DOI: 10.1016/j.cub.2018.05.045