Neuroprotective potential of three neuropeptides PACAP, VIP and PHI.
Journal Title: Pharmacological Reports - Year 2005, Vol 57, Issue 3
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP), vasoactiveintestinal peptide (VIP) and peptide histidine-isoleucine (PHI), are structurally related endogenouspeptides widely expressed in the central and peripheral nervous system and showing rich profile of biologicalactivities. They act as neurotransmitters, neuromodulators and neurotrophic factors. Recently, theirneuroprotective potential has been revealed in numerous in vitro and in vivo models. Thus, PACAP andVIP protected the cells from neurotoxic effects of ethanol, hydrogen peroxide (H(2)O(2), beta-amyloidand glycoprotein 120 (gp120). Moreover, PACAP showed neuroprotection against glutamate, human prion proteinfragment 106-126 [PrP(106-126)] and C2-ceramide. Both peptides reduced brain damage after ischemia andameliorated neurological deficits in a model of Parkinson's disease. Neuroprotective potential of PHIhas not been thoroughly investigated yet, but several results obtained in the last years do not excludeit. The mechanism underlying neuroprotective properties of PACAP seems to involve activation of adenylylcyclase (AC) -> cyclic adenosine 3',5'-mono-phosphate (cAMP) -> protein kinase A (PKA) and mitogen-activatedprotein (MAP) kinase pathways, and inhibition of caspase-3. PACAP can also, yet indirectly, stimulateastrocytes to release neuroprotective factors, such as regulated upon activation normal T cell expressedand secreted (RANTES) and macrophage inflammatory protein 1 (MIP-1) chemokines. Neuroprotective activityof VIP seems to involve an indirect mechanism requiring astrocytes. VIP-stimulated astrocytes secreteneuroprotective proteins, including activity-dependent neurotrophic factor (ADNF) and activity-dependentneuroprotective protein (ADNP), as well as a number of cytokines. However, in the activated microglia,VIP and PACAP are capable of inhibiting the production of inflammatory mediators which can lead to neurodegenerativeprocesses within the brain. In conclusion, studies carried out on the central nervous system have shownthat PACAP, VIP, and likely PHI, are endowed with a neuroprotective potential, which renders them (ortheir derivatives) promising therapeutic agents in several psychoneurological disorders linked to neurodegeneration.
Authors and Affiliations
Agnieszka Dejda, Paulina Sokołowska, Jerzy Nowak
Keywords
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