Human glutaminyl cyclase: Structure, function, inhibitors and involvement in Alzheimer's disease

Pharmacol Res. 2019 Sep:147:104342. doi: 10.1016/j.phrs.2019.104342. Epub 2019 Jul 6.

Abstract

Human glutaminyl cyclase (hQC) is an important enzyme for post-translational modification by converting the N-terminal glutaminyl and glutamyl into pyroglutamate (pGlu) through cyclization. The two isoforms of hQC, secretory glutaminyl cyclase (sQC) and golgi resident glutaminyl cyclase (gQC), are involved in various pathological conditions especially in Alzheimer's disease (AD). The sQC is known to mediate the formation of pyroglutamate containing amyloid beta (pGlu-Aβ) peptides while gQC mediates the maturation of C-C motif chemokine ligand 2 (CCL2). Therefore, hQC (both sQC and gQC) inhibition is considered to be an attractive strategy to prevent the formation of pGlu-Aβ and to reduce neuroinflammation and hence provides a new opportunity for the treatment of AD. In this review, we summarize our current understanding on the structure, function and inhibitors of hQC and its involvement in Alzheimer's disease.

Keywords: Alzheimer’s disease; CCL2; Golgi resident glutaminyl cyclase; Human glutaminyl cyclase; Pyroglutamate; Secretory glutaminyl cyclase; pGlu-Aβ peptide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Aminoacyltransferases* / antagonists & inhibitors
  • Aminoacyltransferases* / chemistry
  • Aminoacyltransferases* / genetics
  • Aminoacyltransferases* / metabolism
  • Animals
  • Humans
  • Neuroprotective Agents / therapeutic use
  • Protein Conformation

Substances

  • Neuroprotective Agents
  • Aminoacyltransferases
  • glutaminyl-peptide cyclotransferase