ER stress and the unfolded protein response in neurodegeneration.

Hetz, Claudio; Saxena Seidel, Smita (2017). ER stress and the unfolded protein response in neurodegeneration. Nature reviews. Neurology, 13(8), pp. 477-491. Nature Publishing Group 10.1038/nrneurol.2017.99

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The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation. ER stress triggers a signalling reaction known as the unfolded protein response (UPR), which induces adaptive programmes that improve protein folding and promote quality control mechanisms and degradative pathways or can activate apoptosis when damage is irreversible. In this Review, we discuss the latest advances in defining the functional contribution of ER stress to brain diseases, including novel evidence that relates the UPR to synaptic function, which has implications for cognition and memory. A complex concept is emerging wherein the consequences of ER stress can differ drastically depending on the disease context and the UPR signalling pathway that is altered. Strategies to target specific components of the UPR using small molecules and gene therapy are in development, and promise interesting avenues for future interventions to delay or stop neurodegeneration.

Item Type:

Journal Article (Review Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Saxena Seidel, Smita


600 Technology > 610 Medicine & health




Nature Publishing Group




Stefanie Hetzenecker

Date Deposited:

22 Sep 2017 11:23

Last Modified:

22 Sep 2017 11:28

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