Cyclic dipeptides: from bugs to brain

Trends Mol Med. 2014 Oct;20(10):551-8. doi: 10.1016/j.molmed.2014.08.003. Epub 2014 Sep 9.


Cyclic dipeptides (CDPs) are a group of hormone-like molecules that are evolutionarily conserved from bacteria to humans. In bacteria, CDPs are used in quorum sensing (QS) to communicate information about population size and to regulate a behavioural switch from symbiosis with their host to virulence. In mammals, CDPs have been shown to act on glial cells (macrophage-like cells) to control a conceptually homologous behavioural switch between homeostatic and inflammatory modes, with implications for the control of neurodegenerative disease. Here we argue that, because of their capacity to regulate inflammation via glial cells and induce a protective response in neuronal cells, CDPs have potential therapeutic utility in an array of inflammatory diseases.

Keywords: diketopiperazines; neurodegeneration; neuroinflammation; neuroprotection; quorum sensing.

MeSH terms

  • Animals
  • Bacteria / metabolism*
  • Biological Transport
  • Brain / metabolism*
  • Central Nervous System / metabolism
  • Dipeptides / chemistry
  • Dipeptides / pharmacology
  • Dipeptides / physiology*
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Microbiota / physiology
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / physiology*
  • Piperazines / metabolism
  • Quorum Sensing


  • Dipeptides
  • Peptides, Cyclic
  • Piperazines
  • histidyl-proline diketopiperazine