peptide-phi and Neurodegenerative-Diseases

Peptide histidine-isoleucine (PHI) and its human analogue peptide histidine-methionine (PHM) are members of a superfamily of structurally related peptides embracing, among others, pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), peptide histidine-valine (PHV), and helodermin. All the peptides display a pleiotropic biological activity. PHI, PHM, PHV and VIP are co-synthesized from the same precursor and share high levels of structural and functional similarity. These peptides may act through common receptors and are widely distributed throughout the body tissues (the central nervous system, gastrointestinal tract, respiratory system, and reproductive system); however, their role remains largely unknown. Changes in the levels of the peptides in the course of different diseases suggest their possible importance and usefulness in diagnostics. Moreover, the neurotrophic and neuroprotective properties of PHI suggest, by analogy to VIP or PACAP, its therapeutic potential in many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

Topics: Amino Acid Sequence; Animals; Cattle; Chickens; Fishes; Humans; Mice; Molecular Sequence Data; Neurodegenerative Diseases; Peptide PHI; Rats; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Species Specificity; Swine; Turkey

Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and peptide histidine-isoleucine (PHI) belong to a structurally related family of polypeptides present in many regions of the central and peripheral nervous system. The neuroprotective potential of PACAP, VIP, and PHI has become a matter of intensive investigations in many animal models. In vitro studies revealed that PACAP protects neurons against apoptosis occurring naturally during CNS development and apoptosis induced by a series of neurotoxins, such as ethanol, hydrogen peroxide (H2O2), prion protein, beta-amyloid, HIV envelope glycoprotein (gp120), potassium ion deficit, and high glutamate concentrations. Similarly, in vivo investigations conducted in models of ischemia and Parkinson's disease confirmed the neuroprotective properties of PACAP. It was revealed that the anti-apoptotic action of PACAP can be directly associated with the activation of signal transduction pathways preventing apoptosis in neurons or involve glial cells capable of releasing other neuroprotective factors affecting neurons. In contrast to PACAP, the neuroprotective action of VIP depends mainly on stimulation of astrocytes to produce and secrete factors of extremely high neuroprotective potential, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP). It was shown that ADNF and ADNP, as well as their shortened derivatives ADNF-9 and NAP, prevent neurons from electrical blockade, excitotoxicity, apoE deficiency, glucose deficit, ischemia, toxic action of ethanol, beta-amyloid, and gp120. The neuroprotective potential of PHI has not been as thoroughly investigated yet, but recent data have confirmed that this peptide can also function as a neuroprotectant. It is thought that PACAP, VIP, and possibly PHI may serve as a goal of modern therapeutic strategies in various neurodegenerative disorders.

Topics: Animals; Central Nervous System; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Peptide PHI; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide