Adaptive preconditioning in neurological diseases – therapeutic insights from proteostatic perturbations.

Le 02 Nov 2021

Auteur : Mollereau B, Rzechorzek NM, Roussel BD, Sedru M, Van den Brink DM, 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

Année : 2016

Journal : Brain Res 1872-6240

PubMed Id : 26923166

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.