Affiliations: [a] Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir, Buenos Aires, Argentina
| [b] Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Correspondence:
[*]
Correspondence to: Eduardo M. Castaño, Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir, Patricias Argentinas 435 Av, Buenos Aires C1405BWE, Argentina. Tel.: +54 11 5238 7500; Fax: +54 11 5238 7501; E-mail: [email protected].
Note: [1] Present address: Instituto de Química y Fisicoquímica Bio-lógicas, CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Note: [2] These authors contributed equally to this work.
Abstract: 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 capable of triggering endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). In metazoans, full activation of a complex ER-UPR network may restore proteostasis and ER function or, if stress cannot be solved, 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.
Keywords: Dementia, endoplasmic reticulum stress, tau proteins, tauopathies, unfolded protein response
