The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration

Int J Mol Sci. 2024 Apr 23;25(9):4581. doi: 10.3390/ijms25094581.

Abstract

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent forms of neurodegeneration. To date, a substantial body of experimental evidence has strongly implicated hypoxia in the pathogenesis of numerous neurological disorders, including AD, PD, and other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) is a transcription factor that triggers a cell survival program in conditions of oxygen deprivation. The involvement of HIF-1α in neurodegenerative processes presents a complex and sometimes contradictory picture. This review aims to elucidate the current understanding of the interplay between hypoxia and the development of AD and PD, assess the involvement of HIF-1 in their pathogenesis, and summarize promising therapeutic approaches centered on modulating the activity of the HIF-1 complex.

Keywords: Alzheimer’s disease; HIF-1; PHD; Parkinson’s disease; hypoxia; neurodegeneration; neuroprotection.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Homeostasis*
  • Humans
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1 / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Oxygen* / metabolism
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / pathology

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen