Cis p-Tau Mediates Neurodegeneration Upon Hypo-thermia

Background: Alzheimer’s disease is the sixth leading cause of death globally and is a multifactorial disorder. Misprocessed amyloid precursor protein and hyper-phosphorylated tau are the major pathological hallmarks playing part in AD. It is clear that hypothermia results in AD the mechanism of which has remained unsecure thus far. It has been recently reported that phosphorylated tau at Thr231 exists in the two distinct cis and trans conformations; whose conversion is being mediated by Pin1 isomerase. Pin1 converts cis to trans species and its sup-pression reflects cis p-tau accumulation and neurodegeneration. We herein examined if hypothermia may suppress Pin1 func-tion.Materials and Methods: In this study, we examined hypother-mia effects on cis p-tau accumulation in SH-SY5Y cells using immunoflourescent (IF) and western blotting (WB) techniques. We treated 5 cell groups under 5 different temperature condi-tion 39,37,30,20 and 15 degrees Celsius in tree times 24,48,72 hours. Also,the expression level of Pin1 enzyme was assessed using real time polymerase change reaction (RT-PCR).Results: We found hypothermia induces cis p-tau accumula-tion and neurodegeneration in cultured cells.Morever, we de-termined that Pin1 is being inhibited upon hypothermia wherby reflecting cis p-tau accumulation and neurodegeneration.Conclusion: Our findings unravel tauopathy mysteries upon hypothermia and would help us find and efficient therappan of patients; likely through immunotherapy with cis pT231-tau monoclonal antibody.

کلیدواژه ها:

Alzheimer’s Disease ، Hypothermia ، Tauopathy ، Cis P-Tau