Adaptive preconditioning in neurological diseases – therapeutic insights from proteostatic perturbations

Bertrand Mollereau, N. M. Rzechorzek, B. D. Roussel, M. Sedru, D. M. Van den Brink, B. Bailly-Maitre, F. Palladino, D. B. Medinas, P. M. Domingos, S. Hunot, S. Chandran, S. Birman, T. Baron, D. Vivien, C. B. Duarte, Hyung Don Ryoo, Hermann Steller, F. Urano, E. Chevet, G. KroemerA. Ciechanover, E. J. Calabrese, R. J. Kaufman, C. Hetz

Research output: Contribution to journalReview articlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)603-616
Number of pages14
JournalBrain Research
Volume1648
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Autophagy
  • ER stress
  • Glioblastoma
  • Hormesis
  • Ischemia
  • Parkinson׳s disease
  • Proteasome
  • Wolfram syndrome

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