biostudies-literatureSilva JMNIA NIH HHSNIEHS NIH HHSNINDS NIH HHS1411-1427https://www.ebi.ac.uk/biostudies/studies/S-EPMC6748085biostudies-literatureUnknown26(8)Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies. Consistent with suggestions that lifetime stress may be an important AD precipitating factor, we previously reported that environmental stress and high glucocorticoid (GC) levels induce accumulation of aggregated Tau; however, the molecular mechanisms for such process remain unclear. Herein, we monitor a novel interplay between RNA-binding proteins (RBPs) and autophagic machinery in the underlying mechanisms through which chronic stress and high GC levels impact on Tau proteostasis precipitating Tau aggregation. Using molecular, pharmacological and behavioral analysis, we demonstrate that chronic stress and higCell death and differentiationDysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology.PMC6748085RF1 AG061706P30 AG013846RF1 AG056318R01 AG050471R01 ES020395R01 AG064932R01 NS089544Sousa NRodrigues SSilva JMDioli CMazuik BFTakashima ALudovico PGomes PNeves-Carvalho AWolozin BSoares-Cunha CSotiropoulos ISampaio-Marques BfalseDysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology.Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies. Consistent with suggestions that lifetime stress may be an important AD precipitating factor, we previously reported that environmental stress and high glucocorticoid (GC) levels induce accumulation of aggregated Tau; however, the molecular mechanisms for such process remain unclear. Herein, we monitor a novel interplay between RNA-binding proteins (RBPs) and autophagic machinery in the underlying mechanisms through which chronic stress and high GC levels impact on Tau proteostasis precipitating Tau aggregation. Using molecular, pharmacological and behavioral analysis, we demonstrate that chronic stress and hig2019-01-01T00:00:00Z2019 Aug2025-04-19T04:29:14.786Z2025-04-19T04:29:14.786ZS-EPMC67480853044294810.1038/s41418-018-0217-1