Intracellular peptides as drug prototypes

Mayara C.F. Gewehr, Ami Navon, Emer S. Ferro

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Proteasome-processed functional intracellular peptides (InPeps) were recently described, suggesting the need for adapting our understanding of how cells build macromolecular signaling interactions. InPeps are distinct from antigens, cryptides and neuropeptides, having been initially identified in mammals by means of a substrate-capture assay that used inactive endo-oligopeptidases. InPeps modulate G-protein coupled receptor signal transduction, cell survival and energy metabolism after direct delivery within cells. In neurodegenerative diseases, for example, InPep profiles were modified in parallel with disease progression. Manipulation of oligopeptidase metabolic activity through knockdown, overexpression or genetic knockout animal models alters specific InPep profiles, with corresponding phenotypic alterations. InPep structure can also be modified to develop novel therapeutic drugs, as demonstrated here for the example of pep19. In this chapter, we review findings that precipitated the original discovery of InPeps as well as the rationale for use of InPeps as drug prototypes.

Original languageEnglish
Title of host publicationPeptide and Peptidomimetic Therapeutics
Subtitle of host publicationFrom Bench to Bedside
EditorsNir Qvit, Samuel J.S. Rubin
Number of pages35
ISBN (Electronic)9780128201411
ISBN (Print)9780128204474
StatePublished - 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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