Pituitary Adenylyl Cyclase Activating Polypeptide (PACAP) Signaling and the Cell Cycle Machinery in Neurodegenerative Diseases

Curr Pharm Des. 2018;24(33):3878-3891. doi: 10.2174/1381612825666181127102311.


Pituitary adenylyl cyclase activating polypeptide (PACAP) is a neuropeptide with great neuroprotective effects and remarkable therapeutic potential. PACAP activates several cellular pathways to exert its protective effects. Emerging evidence shows that PACAP can modify the levels and activity of cell cycle components involved in neurodegeneration to protect neurons from death. Cell cycle is a highly regulated process that controls the balance between proliferation, differentiation and death of every cell in the body. Aberrant expression and function of components of the cell cycle machinery have been linked to neurodegenerative diseases, in which different types of neuronal cells become dysfunctional and die in response to toxic insults. Since neurons are postmitotic cells, re-entry into the cell cycle has been shown to be pathological and contributes to the process of neurodegeneration. Moreover, an increasing number of studies highlight the importance of the role of cell cycle components outside the cell cycle and their involvement in neurodegenerative disorders. Here, we discuss the pleiotropic effects of PACAP on cell cycle machinery and the implication for the treatment of neurodegenerative diseases.

Keywords: Neurodegeneration; adult neurons; apoptosis; cell cycle re-entry; pituitary adenylyl cyclase activating polypeptide (PACAP); therapy..

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / drug effects*
  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*
  • Signal Transduction / drug effects*


  • Pituitary Adenylate Cyclase-Activating Polypeptide