Title:Pituitary Adenylyl Cyclase Activating Polypeptide (PACAP) Signaling and the Cell Cycle Machinery in Neurodegenerative Diseases
Volume: 24
Issue: 33
Author(s): María José Polanco*Maria Pennuto*
Affiliation:
- Laboratory of Pharmacology and Toxicology, Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, San Pablo CEU University, Madrid,Spain
- Department of Biomedical Sciences, University of Padova, 35100 Padova,Italy
Keywords:
Neurodegeneration, cell cycle re-entry, pituitary adenylyl cyclase activating polypeptide (PACAP), apoptosis, therapy, adult
neurons.
Abstract: 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.
