Dynamics of Internalization and Intracellular Interaction of Tau Antibodies and Human Pathological Tau Protein in a Human Neuron-Like Model.

ABSTRACT: We and others have shown in various in vivo, ex vivo and cell culture models that several tau antibodies interact with pathological tau within neurons. To further clarify this interaction in a dynamic human model, we differentiated SH-SY5Y cells with retinoic acid and BDNF to create a neuron-like model. Therein, tau antibodies were primarily taken up by receptor-mediated endocytosis, and prevented toxicity of human brain-derived paired helical filament-enriched tau (PHF). Subsequently, we monitored in real-time the interaction of antibodies and PHF within endocytic cellular compartments. Cells were pre-treated with fluorescently-tagged PHF and then incubated with tau antibodies, 4E6, 6B2, or non-specific isotype control IgG1 labeled with a pH sensitive dye. The uptake and binding of

SUBMITTER: Shamir DB 

PROVIDER: S-EPMC7727311 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature