The potential relevaceof neuropeptide Y (NPY) and NPY receptors in neuroprotection
Neuropeptide Y (NPY) is a 36-amino acid neurotransmitter and neuromodulator widely distributed in the mammalian central and peripheral nervous system and has been associated with a number of physiological and pathological conditions. In the forebrain this peptide is preferentially expressed in interneurons and modulates, mainly inhibits, the release of other neurotransmitters. NPY acts on specific receptors coupled to G-proteins, and 6 types of NPY receptors (Y1 to Y6) have been identified based on different pharmacological profiles. It has been well documented that NPY inhibits glutamatergic transmission and decreases hippocampal epileptiform activity which may lead to neuroprotection. Our earlier studies demonstrated the neuroprotective activity of NPY injected into the hippocampus on kainate neurotoxicity in that structure. The neuroprotective action of NPY against excitotoxicity was also shown in neuronal cultures. Studies with specific Y receptor ligands revealed a crucial role of Y2 and Y5 receptors. Activation of those receptors diminished neuronal excitotoxic degenerations both in vitro and in vivo, but no protective effect was observed after Y1 agonist. One of the most promising finding of our study is that NPY or Y2 and Y5 ligands exert a significant neuroprotective effect after delayed treatment, 3 – 6 h after the onset of intoxication. Much less in known about the protective action of NPY on ischemic damage, both in vitro and in vivo, but some positive effects were also found. The role of NPY in chronic neurodegenerations such as Alzheimer, Parkinson and Huntington diseases has also been postulated but the results are divergent and unclear. Summing up, our data and other authors studies indicate the neuroprotective properties of NPY; moreover, the effectiveness of delayed treatment may open up a future possibility of the potential therapeutic use of such compounds in patients.
Rekord w opracowaniu