Amino Acids

, Volume 35, Issue 2, pp 283–289 | Cite as

Focus on cyclo(His-Pro): history and perspectives as antioxidant peptide

  • A. Minelli
  • I. Bellezza
  • S. Grottelli
  • F. Galli
Minireview Article


Cyclo(His-Pro) is an endogenous cyclic dipeptide structurally related to tyreotropin-releasing hormone that was originally discovered in brain. In the central nervous system it has been described to exert multiple biological activities, which seem to be related to a presynaptic dopaminergic mechanism and include among the others a leptin-like function. It can be found in several body fluids and in the gastrointestinal tract where it has been suggested to act as a gut peptide with influence on the entero-insular axis. The oral administration of cyclo(His-Pro) and zinc was described to improve with a synergistic mechanism the glycaemic control in diabetes.

The most intriguing function of this cyclic dipeptide is related with its neuroprotective role that was first reported in traumatic injuries of the spinal cord, and then confirmed in other models of experimental injuries of the nervous system. The mechanism that lies behind the neuroprotective activity of cyclo(His-Pro) remain poorly understood. Recent in vitro studies on rat pheochromocytoma PC12 cells have shown that it is a protective factor against stress stimuli and there is early pre-clinical evidence strongly suggesting that it enhances the expression of small heat shock proteins and antioxidant protection at the cellular level.

Future research is underway to better characterize the possible use of this cyclic dipeptide in the therapy of neurodegenerative and metabolic disorders.

Keywords: CHP – Presynaptic dopaminergic mechanism – Diabetes – ERK 1/2 – p-38MAPK – Small hsp – Neuroprotection 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • A. Minelli
    • 1
  • I. Bellezza
    • 1
  • S. Grottelli
    • 1
  • F. Galli
    • 2
  1. 1.Dipartimento Medicina Sperimentale Scienze Biochimiche, Sezione Biochimica CellulareUniversità di Perugia, Via del GiochettoPerugiaItaly
  2. 2.Dipartimento Medicina Interna, Sezione Biochimica Applicata e Scienze della NutrizioneUniversità di Perugia, Via del GiochettoPerugiaItaly

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