The Aryl Hydrocarbon Receptor: A Mediator and Potential Therapeutic Target for Ocular and Non-Ocular Neurodegenerative Diseases

Int J Mol Sci. 2020 Sep 16;21(18):6777. doi: 10.3390/ijms21186777.

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which senses environmental, dietary or metabolic signals to mount a transcriptional response, vital in health and disease. As environmental stimuli and metabolic products have been shown to impact the central nervous system (CNS), a burgeoning area of research has been on the role of the AHR in ocular and non-ocular neurodegenerative diseases. Herein, we summarize our current knowledge, of AHR-controlled cellular processes and their impact on regulating pathobiology of select ocular and neurodegenerative diseases. We catalogue animal models generated to study the role of the AHR in tissue homeostasis and disease pathogenesis. Finally, we discuss the potential of targeting the AHR pathway as a therapeutic strategy, in the context of the maladies of the eye and brain.

Keywords: aryl hydrocarbon receptor; inflammation; neurodegeneration; retinal diseases; transcription factor.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / agonists
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Biotransformation
  • Central Nervous System / cytology
  • Central Nervous System / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / physiology
  • Disease Models, Animal
  • Eye Diseases / drug therapy
  • Eye Diseases / genetics
  • Eye Diseases / metabolism*
  • Eye Proteins / physiology
  • Gene Expression Regulation
  • Helix-Loop-Helix Motifs
  • Humans
  • Ligands
  • Mammals / metabolism
  • Molecular Targeted Therapy*
  • Multiple Sclerosis / drug therapy
  • Nerve Degeneration
  • Nerve Tissue Proteins / physiology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Parkinson Disease / metabolism
  • Polychlorinated Dibenzodioxins / pharmacology
  • Quinolones / pharmacology
  • Quinolones / therapeutic use
  • Rats
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / physiology*
  • Signal Transduction / physiology
  • Transcription, Genetic
  • Xenobiotics / metabolism

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Ligands
  • Nerve Tissue Proteins
  • Polychlorinated Dibenzodioxins
  • Quinolones
  • Receptors, Aryl Hydrocarbon
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • laquinimod