Hypoxic adaptation in the nervous system: Promise for novel therapeutics for acute and chronic neurodegeneration Review uri icon

Overview

MeSH Major

  • Adaptation, Physiological
  • Hypoxia
  • Nerve Degeneration
  • Nervous System

abstract

  • Homeostasis is the process by which cells adapt to stress and prevent or repair injury. Unique programs have evolved to sense and activate these homeostatic mechanisms and as such, homeostatic sensors may be potent therapeutic targets. The hypoxic response mediated by hypoxia inducible factor (HIF) downstream of oxygen sensing by HIF prolyl 4-hydroxylases (PHDs) has been well-studied, revealing cell-type specific regulation of HIF stability, activity, and transcriptional targets. HIF's paradoxical roles in nervous system development, physiology, and pathology arise from its complex roles in hypoxic adaptation and normoxic biology. Understanding how to engage the hypoxic response so as to recapitulate the protective mechanism of ischemic preconditioning is a high priority. Indeed, small molecules that activate the hypoxic response provide broad neuroprotection in several clinically relevant injury models. Screens for PHD inhibitors have identified novel therapeutics for neuroprotection that are ready to proceed to clinical trials for ischemic stroke. Better understanding the mechanisms of how to engage hypoxic adaption without altering development or physiology may identify additional novel therapeutic targets for diverse acute and chronic neuropathologies.

publication date

  • January 2016

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1007/978-1-4899-7678-9_16

PubMed ID

  • 27343100

Additional Document Info

start page

  • 221

end page

  • 43

volume

  • 903