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Amino Acids

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Structural properties and role of the endocannabinoid lipases ABHD6 and ABHD12 in lipid signalling and disease

  • Laura Kind
  • Petri KursulaEmail author
Invited Review

Abstract

The endocannabinoid (eCB) system is an important part of both the human central nervous system (CNS) and peripheral tissues. It is involved in the regulation of various physiological and neuronal processes and has been associated with various diseases. The eCB system is a complex network composed of receptor molecules, their cannabinoid ligands, and enzymes regulating the synthesis, release, uptake, and degradation of the signalling molecules. Although the eCB system and the molecular processes of eCB signalling have been studied extensively over the past decades, the involved molecules and underlying signalling mechanisms have not been described in full detail. An example pose the two poorly characterised eCB-degrading enzymes α/β-hydrolase domain protein six (ABHD6) and ABHD12, which have been shown to hydrolyse 2-arachidonoyl glycerol—the main eCB in the CNS. We review the current knowledge about the eCB system and the role of ABHD6 and ABHD12 within this important signalling system and associated diseases. Homology modelling and multiple sequence alignments highlight the structural features of the studied enzymes and their similarities, as well as the structural basis of disease-related ABHD12 mutations. However, homologies within the ABHD family are very low, and even the closest homologues have widely varying substrate preferences. Detailed experimental analyses at the molecular level will be necessary to understand these important enzymes in full detail.

Keywords

Endocannabinoid signalling α/β-hydrolase 2-Arachidonoyl glycerol Lipid metabolism PHARC 

Notes

Acknowledgements

This study was supported by a training grant from the ERASMUS + programme.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Data availability

The data generated and analysed during the current study are available from the corresponding author upon reasonable request.

Supplementary material

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Supplementary material 2 (TIFF 6682 kb)
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© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiomedicineUniversity of BergenBergenNorway
  2. 2.Faculty of Biochemistry and Molecular MedicineUniversity of OuluOuluFinland

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