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Curr Pharm Des. 2018 Nov 26. doi: 10.2174/1381612825666181127102311. [Epub ahead of print]

Pituitary adenylyl cyclase activating polypeptide (PACAP) signaling and the cell cycle machinery in neurodegenerative diseases.

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Laboratory of Pharmacology and Toxicology, Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, CEU San Pablo University, Madrid. Spain.
Dulbecco Telethon Institute, Centre for Integrative Biology (CIBIO), University of Trento, 38100 Trento. Italy.


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 dye in response to toxic insults. Since neurons are post-mitotic cells, re-entry into the cell cycle has been shown to be pathological and contribute to the process of neurodegeneration. Moreover, an increasing number of studies highlights 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.


adult neurons; apoptosis; cell cycle re-entry; neurodegeneration; pituitary adenylyl cyclase activating polypeptide (PACAP); therapy

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