A Discovery to Figure out Toxicity Mechanism in TBI Models

Background: Traumatic brain injury (TBI) has been suggestedas the biggest risk factor for chronic neurodegenerative disorders;such as Alzheimer’s disease and amyotrophic lateral sclerosis.It has been shown that phosphorylated tau at Thr۲۳۱ inthe cis conformation is the central mediator of cell death upontauopathy. Besides, cis p-tau is being considered as the earliesttau epitope; ahead of any oligomer, aggregate and tangleepitopes, resulting in cell death. Also, neurons treated with TBIbrain lysates had much higher rate of apoptosis. Thus, cis p-tauis indeed neurotoxic and plays key role in neurodegenerationupon tauopathy and TBI.Materials and Methods: To test the hypothesis, TBI mousebrains were immunostained with cis p-tau.Results: We have found that neurotoxic cis p-tau initially movesinto nucleus in the TBI brains; causing cell death in a time dependentmanner. Thus, we hypothesized that cis p-T۲۳۱-tau isbecoming neurotoxic upon its nuclear translocation. To test thehypothesis, TBI mouse brains were immunostained with cis ptau.Our results demonstrated that the neurotoxic cis, but nottrans, pT۲۳۱-tau moves into nucleus. Furthermore, cis p-tauplays its pathogenic roles upon its translocation.Conclusion: Taking these together, we concluded that cis p-taukills the cells through some physiological processes interruption;likely by interacting with nuclear factors. Our data opennew windows toward understanding tauopathy and TBI molecularmechanisms and further may shed light to possible treatmentsfor neurodegenerative disorders.

کلیدواژه ها:

TBI ، Tauopathy ، Neurodegeneration ، Cis p-tau