Journal of Molecular Neuroscience

, Volume 36, Issue 1–3, pp 26–37 | Cite as

Inhibitory Effect of PACAP on Caspase Activity in Neuronal Apoptosis: A Better Understanding Towards Therapeutic Applications in Neurodegenerative Diseases

  • Agnieszka Dejda
  • Valérie Jolivel
  • Steve Bourgault
  • Tommy Seaborn
  • Alain Fournier
  • Hubert VaudryEmail author
  • David VaudryEmail author


Programmed cell death, which is part of the normal development of the central nervous system, is also implicated in various neurodegenerative disorders. Cysteine-dependent aspartate-specific proteases (caspases) play a pivotal role in the cascade of events leading to apoptosis. Many factors that inhibit cell death have now been identified, but the underlying mechanisms are not fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neurotrophic activities during development and to prevent neuronal apoptosis induced by various insults such as ischemia. Most of the neuroprotective effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression, which inhibits cytochrome c release and blocks the activation of caspases. The inhibitory effect of PACAP on the apoptotic cascade suggests that selective, stable, and potent PACAP derivatives could potentially be of therapeutic value for the treatment of post-traumatic and/or chronic neurodegenerative processes.


Apoptosis Caspase PACAP Neuroprotection 



Supported by INSERM (U413), the European Institute for Peptide Research (IFRMP23), the Regional Platform for Cell Imaging (PFRRICHN), the National Research Agency (ANR-06-JCJC-0071), the Institut pour la Recherche sur la Moelle épinière et l′Encéphale (IRME), the Institut de Recherches Scientifiques sur les Boissons (IREB), and the Conseil Régional de Haute-Normandie. A.D. is the recipient of a postdoctoral fellowship from the Fondation pour la Recherche Médicale. V.J. is the recipient of a Convention Industrielle de Formation par la Recherche (CIFRE). S.B. is the recipient of a doctoral studentship from the Natural Sciences and Engineering Research Council of Canada. T.S. is the recipient of a postdoctoral fellowship from INSERM. H.V. is Affiliated Professor at the INRS-Institute Armand-Frappier (Montreal, Canada).


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Copyright information

© Humana Press 2008

Authors and Affiliations

  • Agnieszka Dejda
    • 1
    • 2
    • 3
    • 4
  • Valérie Jolivel
    • 1
    • 2
    • 3
    • 5
  • Steve Bourgault
    • 1
    • 2
    • 3
    • 6
  • Tommy Seaborn
    • 1
    • 2
    • 3
  • Alain Fournier
    • 3
    • 6
  • Hubert Vaudry
    • 1
    • 2
    • 3
    Email author
  • David Vaudry
    • 1
    • 2
    • 3
    Email author
  1. 1.INSERM U413, Laboratory of Cellular and Molecular NeuroendocrinologyMont-Saint-AignanFrance
  2. 2.European Institute for Peptide Research (IFRMP 23)University of RouenMont-Saint-AignanFrance
  3. 3.International Associated Laboratory Samuel de ChamplainMont-Saint-AignanFrance
  4. 4.Institute for Medical BiologyPolish Academy of SciencesLodzPoland
  5. 5.QUIDD (QUantitative Imaging in Drug Development)Saint-Etienne-du-RouvrayFrance
  6. 6.INRS—Institut Armand-FrappierInstitut National de la Recherche Scientifiquedes PrairiesCanada

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