Behind the curtain of tauopathy: a show of multiple players orchestrating tau toxicity

摘要: tau, a microtubule-associated protein, directly binds with microtubules to dynamically regulate the organization of cellular cytoskeletons, and is especially abundant in neurons central nervous system. Under disease conditions such as Pick's disease, progressive supranuclear palsy, frontotemporal dementia, parkinsonism linked chromosome 17 Alzheimer's tau proteins can self-assemble paired helical filaments progressing neurofibrillary tangles. In these diseases, collectively referred "tauopathies", alterations diverse modifications including phosphorylation, metal ion binding, glycosylation, well structural changes have all been observed, indicating complexity variability factors regulation toxicity. Here, we review our current knowledge hypotheses from relevant studies on toxicity, emphasizing roles phosphorylations, ions, folding clearance control underlining etiology their regulations. A summary clinical efforts associated findings drug candidates under development also presented. It hoped that more comprehensive understanding will provide us better blueprint networking neuronal cells offer hints for design efficient strategies tackle tau-related diseases future.