ABHD6: Its Place in Endocannabinoid Signaling and Beyond

Trends Pharmacol Sci. 2019 Apr;40(4):267-277. doi: 10.1016/j.tips.2019.02.002. Epub 2019 Mar 7.

Abstract

The endocannabinoid (eCB) signaling system modulates neurotransmission and inflammation, among other physiological functions. Its newest member, α/β-hydrolase domain-containing 6 (ABHD6), has emerged as a promising therapeutic target to treat several devastating diseases, including epilepsy. Here, we review the molecular mechanisms that mediate and control eCB signaling and, within it, the specific role of ABHD6. We also discuss how ABHD6 controls the abundance of additional lipids and the trafficking of ionotropic receptors to plasma membranes. We finish with several unexplored questions regarding this novel enzyme. Our current understanding of the molecular mechanism and biological function of ABHD6 provides a strong foundation for the development of small-molecule therapeutics to treat devastating diseases.

Keywords: ABHD6; endocannabinoids; enzyme; epilepsy; neuroinflammation; neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Drug Development / methods*
  • Endocannabinoids / metabolism*
  • Epilepsy / drug therapy
  • Epilepsy / physiopathology
  • Humans
  • Monoacylglycerol Lipases / metabolism*
  • Signal Transduction / physiology
  • Synaptic Transmission / physiology

Substances

  • Endocannabinoids
  • ABHD6 protein, human
  • Monoacylglycerol Lipases