Neurodegenerative diseases are defined as hereditary and sporadic conditions which are characterized by a progressive loss of a structure or functions of neurons. In such disorders neuronal destruction is caused mainly by an abnormal elevated level of one of the primary excitatory neurotransmitters in the mammalian CNS – glutamate 1 . This prolonged and excessive accumulation of glutamate causes over-stimulation of its receptors, especially of the N-methyl-D-aspartate (NMDA) receptor, which in consequence leads to excitotoxicity, a process well seen in CA1 area, which is known to be the hippocampal region most sensitive to excitotoxicity. According to that, several endogenous peptides have been studied for their neuroprotective profile.
The tridecapeptide neurotensin (NT) is known from the ability to induce naloxone-insensitive analgesic responses after brain injection 2 , which makes it a promising target in treatment of various pain states. Unfortunately, NT plays an important role as a neurodegenerative factor by significantly increasing glutamate release in discrete rat brain regions and intensifying NMDA-mediated glutamate signaling 3 . In contrary, our as well as others recent study regarding an opioid peptide indicated that opioids have neuroprotective behavior following NMDA exposure 4,5 .
This information prompted us to combine an opioid and neurotensin into one entity hoping that an opioid pharmacophore may make a modulatory impact on neurotensin‘s neurodegenerative activity. This step seems to be understood according to our previous study reporting that a chemical hybridization of opioid and neurotensin pharmacophores resulted in hypersynergism between both parts of the novel chimera 6 .
The aim of the presented study was to investigate the possible neuroprotective effects of PK20 opioid-neurotensin hybrid peptide on glutamate-mediated CA1 region cell death in comparison with its opioid element as well as with neurotensin.
Acknowledgment: This work has been supported by NCN Grant:2011/03/N/NZ4/02417