MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons

In this study, we investigated the impact of MSUT2 on tau pathogenesis using tau seeding models. Our findings indicate t hat the loss of MSUT2 mitigates human tau seed-induced pathology in neuron cultures and mouse models. In addition, MSUT2 regulates many gene transcripts, including the Adenosine Receptor 1 (A1AR), and we show that down regulation or inhibition of A1AR modulates the activity of the “ArfGAP with SH3 Domain, Ankyrin Repeat, and PH Domain 1 protein” (ASAP1), thereby influencing the internalization of pathogenic tau seeds into neurons resulting in reduction of tau pathology.

http://link.springer.com/10.1007/s00401-024-02703-3

Source: Acta Neuropathologica - March 12, 2024 Category: Neurology Source Type: research