Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme

Int J Mol Sci. 2014 Sep 22;15(9):16787-99. doi: 10.3390/ijms150916787.


The term "cryptome" refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cerebral Cortex / enzymology*
  • Insulysin / physiology*
  • Male
  • Mass Spectrometry
  • Models, Biological
  • Molecular Sequence Data
  • Nerve Tissue Proteins / physiology*
  • Peptide Fragments / metabolism
  • Protein Precursors / metabolism*
  • Proteolysis
  • Rats
  • Rats, Wistar
  • Receptors, Neuropeptide / metabolism*
  • Spectrometry, Mass, Electrospray Ionization
  • Surface Plasmon Resonance
  • Tissue Extracts


  • Nerve Tissue Proteins
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Neuropeptide
  • Tissue Extracts
  • neuropeptide FF receptor
  • Insulysin