A simple human cell model for TAU trafficking and tauopathy-related TAU pathology

摘要

The microtubule(MT)-associated protein TAU is highly abundant in the axon of human brain neurons,where it binds to and stabilizes MT filaments.Thereby,TAU regulates the dynamic(dis)assembly of MT strands and is involved in a wide range of neuronal functions.In Alzheimer's disease(AD)and other tauopathies,TAU is missorted into the somatodendritic compartment.TAU missorting is accompanied by(or leads to)abnormal TAU phosphorylation,MT destabilization,and loss of dendritic spines and mitochondria,eventually resulting in TAU aggregation,neuronal dysfunction and cell death(Arendt et al.,2016).Strikingly,the mechanisms of TAU sorting,and the detrimental cascade upon its failure,are still not fully understood.