Normal and Pathological Tau Uptake Mediated by M1/M3 Muscarinic Receptors Promotes Opposite Neuronal Changes.

ABSTRACT: The microtubule associated protein tau is mainly found in the cell's cytosol but recently it was also shown in the extracellular space. In neurodegenerative diseases, like Alzheimer's disease (AD), pathological tau spreads from neuron to neuron enhancing neurodegeneration. Here, we show that HEK293 cells and neurons in culture uptake extracellular normal and pathological Tau. Muscarinic receptor antagonists atropine and pirenzepine block 80% this uptake. CHO cells do not express these receptors therefore cannot uptake tau, unless transfected with M1 and/or M3 receptor. These results strongly suggest that muscarinic receptors mediate this process. Uptake of normal tau in neurons enhances neuronal process formation but a pseudophosphorylated form of tau (pathological human tau, PH-Tau) disru

SUBMITTER: Morozova V 

PROVIDER: S-EPMC6737038 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature