Parkinson's disease in the nuclear age of neuroinflammation

Trends Mol Med. 2013 Mar;19(3):187-96. doi: 10.1016/j.molmed.2012.12.003. Epub 2013 Jan 11.

Abstract

Chronic neuroinflammation is associated with the pathophysiology of Parkinson's disease, a movement disorder characterised by deterioration of the nigrostriatal system of the brain. Recent studies have yielded important insights into the regulation of inflammation by nuclear receptors, a superfamily of ligand-activated transcription factors. Certain nuclear receptors are also emerging as regulators of neurodegeneration, including the degeneration of dopaminergic neurons in Parkinson's disease, and the importance of transcriptional control in this process is becoming increasingly apparent. Here, we discuss the role of Nurr1, peroxisome proliferator-activated receptors (PPARs), retinoic acid receptors, and glucocorticoid receptors in neuroinflammatory processes that contribute to dopaminergic neuronal degeneration. We examine current evidence providing insight into the potential of these important players as therapeutic targets for Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / physiopathology
  • Disease Models, Animal
  • Dopamine
  • Humans
  • Inflammation / physiopathology*
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism
  • Parkinson Disease / physiopathology*
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism

Substances

  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Glucocorticoid
  • Receptors, Retinoic Acid
  • Dopamine