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Adaptive preconditioning in neurological diseases - Therapeutic insights from proteostatic perturbations.

TitleAdaptive preconditioning in neurological diseases - Therapeutic insights from proteostatic perturbations.
Publication TypeJournal Article
Year of Publication2016
AuthorsMollereau B, Rzechorzek NM, Roussel BD, Sedru M, Van den Brink D, Bailly-Maitre B, Palladino F, Medinas DB, Domingos PM, Hunot S, Chandran S, Birman S, Baron T, Vivien D, Duarte CB, Ryoo HD, Steller H, Urano F, Chevet E, Kroemer G, Ciechanover A, Calabrese EJ, Kaufman RJ, Hetz C
JournalBrain Res
Date Published2016 Mar 2
ISSN1872-6240
Abstract

In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson's disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses - and the molecular pathways they recruit - might be exploited for therapeutic gain. This article is part of a Special Issue entitled SI:ER stress.

DOI10.1016/j.brainres.2016.02.033
Alternate JournalBrain Res.
PubMed ID26923166
Publication institute
CRM