To Study DAPK1 Effects on Tauopathy in The Stressed out Culture Neurons

Background: Tau abnormal hyperphosphorylation is a major pathological hallmark in neurodegeneration. It has been shown that phosphorylated tau at Thr231 exists in the two distinct cis & trans conformations, in which that cis p-tau is extremely neu-rotoxic and drives neurodegeneration. The conversion of cis p-tau to trans is being mediated by Pin1 isomerase. Pin1 can be inhibited by multiple mechanisms, resulting in cis p-tau ac-cumulation and neurodegeneration. On the other hand, DAPK1 (death associated protein kinase 1), has a key role in the devel-opment of Alzheimer disease; likely through Pin1 suppression. It has been shown that nutrition depletion stress would result in cis p-tau accumulation in SH-SY5Y cells. We herein examine if DAPK1 inhibition may stop cis p-tau accumulation in the cells. Materials and Methods: We immunostained stressed out SH-SY5Y cells in both treated and untreated with DAPK1 inhibi-tor with cis pT231-tau monoclonal antibody. Also, by Western Blotting Technique, we studied the amounts of cis p-tau and Pin1 in the both groups.Results: We found a cis p-tau increase in stressed out SH-SY5Y cells in a timely manner, leading to the cell death. Importantly, we found that DAPK1 Inhibition leads to a reduced cis p-tau levels as well as suppressed neural cell death.Conclusion: Treating stressed out SH-SY5Y cells with DAPK1 inhibitor not only decreases cis p-tau amounts but also prevents neuronal apoptosis. These results open new windows toward neurodegeneration molecular mechanisms in which DAPK1 plays central role. We believe that DAPK1 inhibitors may have therapeutic implications in cis p-tau reduction and AD treat-ment.

Keywords:

Alzheimer s Disease (AD) , Tauopathy , Pin1 , DAPK1 , DAPK1 Inhibitor