Endoplasmic Reticulum Stress in Tauopathies: Contrasting Human Brain Pathology with Cellular and Animal Models

BOCAI, NADIA I.; MARCORA, MARÍA S.; BELFIORI-CARRASCO, LAUTARO F.; MORELLI, LAURA; CASTAÑO, EDUARDO M.; CASTAÑO, EDUARDO M.

JOURNAL OF ALZHEIMER'S DISEASE

IOS PRESS

Lugar: Amsterdam; Año: 2019

1387-2877

The accumulation and spreading of protein tau in the human brain are major features of neurodegenerative disorders known as tauopathies. In addition to several subcellular abnormalities, tau aggregation within neurons seems capableoftriggeringendoplasmicreticulum(ER)stressandtheconsequentunfoldedproteinresponse(UPR).Inmetazoans, fullactivationofacomplexER-UPRnetworkmayrestoreproteostasisandERfunctionor,ifstresscannotbesolved,commit cells to apoptosis. Due to these alternative outcomes (survival or death), the pharmacological manipulation of ER-UPR has become the focus of potential therapies in many human diseases, including tauopathies. Here we update and analyze the experimental data from human brain, cellular, and animal models linking tau accumulation and ER-UPR. We further discuss mechanistic aspects and put the ER-UPR into perspective as a possible therapeutic target in this group of diseases.