Cis pT231-tau Mediates Neurodegeneration upon Pollution

Background: Alzheimer disease is a neurodegenerative disorder and sixth leading cause of death globally. AD is a multifactorial disease in which genetical background as well as envi-ronmental factor play role in it. Among environmental factors, pollution is of crucial importance considering modern life style. Despite extensive considerations, it remains uncertain how pol-lution mediates neurodegeneration and AD. There are two ma-jor pathological hallmarks playing part in AD, including miss-processed amyloid precursor protein and hyperphosphorylated tau. Tau is a microtubule associated protein the functions of which are thought to be controlled by phosphorylation. Any-how, tau hyperphosphorylation or some post phosphorylation modifications reflects tau pathogenicity. Recent studies have demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformation in which cis pT231-tau is highly neurotoxic and acts as an early driver of tauopathy in several neurodegenerative diseases. We herein studied if Cis pT231-tau has a contribution in neurodegeneration caused by pollution.Materials and Methods: We employed mice model to exam-ine the effect of pollution on the CNS. We studied the mouse brains using immunoflourescent staining and western blotting with conformation specific antibody against cis pT231-tau Results: Fluorescent imaging and western blotting analysis of mouse brains demonstrated a prominent cis p-tau accumulation in pollution treated mouse models compare to control healthy ones.Conclusion: It has been clearly demonstrated that pollution would result in tauopathy but the actual molecular mechanism has remained uncertain thus far. We have demonstrated that pollution would cause cis pT231-tau accumulation in neurons, resulting in neurodegneration. Our findings unravel tauopathy mysteries upon pollution and would help us find a right thera-peutic target to fight the devastating disorder caused by modern life.

Keywords:

Cis pT231-Tau , Neurodegeneration , Pollution