Enkephalin: Difference between revisions

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Marina González Castilla, Borja Fernández García, Michal Harel

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 Met-Enkephalin (MENK) may contribute to immune responses against tumors and viral infections by activating multiple types of immune cells, enabling them to secrete various cytokines or directly kill target cells. The nuclear membrane of certain cancer cells expressed receptors to which MENK bound, resulting in marked growth inhibition of cancer cells in vitro<ref>Wang DM, Wang GC, Yang J, Plotnikoff NP, Griffin N, Han YM, Qi RQ, Gao XH and Shan FP: Inhibition of the growth of human melanoma cells by methionine enkephalin. Mol Med Rep 14: 5521-5527, 2016</ref>.
-Activation of δ opioid receptors acts against oxidative stress in the central nervous system and promotes neuron survival. It is able to cross the blood-brain barrier; it has been hypothesized to be a promising strategy to promote neuron regeneration, especially in brain damage caused by stroke <ref>Liu, Y., Fu, N., Su, J., Wang, X., & Li, X. (2019). Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3. BioMed research international, 2019, 4273290. https://doi.org/10.1155/2019/4273290</ref>. Multifunctional fluorinated enkephalin analog, LYS739 can be considered as a potential lead for ischemic stroke research and may provide advantages given the multimeric peptide-opiate structure<ref>Rashedul Islam, M., Yang, L., Sun Lee, Y., J Hruby, V., T Karamyan, V., & J Abbruscato, T. (2016). Enkephalin-fentanyl multifunctional opioids as potential neuroprotectants for ischemic stroke treatment. Current pharmaceutical design, 22(42), 6459-6468.</ref>.
+Activation of δ opioid receptors acts against oxidative stress in the central nervous system and promotes neuron survival. Enkephalin is able to cross the blood-brain barrier; it has been hypothesized to be a promising strategy to promote neuron regeneration, especially in brain damage caused by stroke <ref>Liu, Y., Fu, N., Su, J., Wang, X., & Li, X. (2019). Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3. BioMed research international, 2019, 4273290. https://doi.org/10.1155/2019/4273290</ref>. Multifunctional fluorinated enkephalin analog, LYS739 can be considered as a potential lead for ischemic stroke research and may provide advantages given the multimeric peptide-opiate structure<ref>Rashedul Islam, M., Yang, L., Sun Lee, Y., J Hruby, V., T Karamyan, V., & J Abbruscato, T. (2016). Enkephalin-fentanyl multifunctional opioids as potential neuroprotectants for ischemic stroke treatment. Current pharmaceutical design, 22(42), 6459-6468.</ref>.
 The main and most known effect of enkephalins is analgesia, which makes the therapeutic use of enkephalins to treat pain one their main clinical relevant aspect. However, enkephalins have a relatively low stability ''in-vivo'', due to their degradation by endogenous peptidases <ref name="cullen"/>. Two approaches have been proposed to this issue: the first one is the chemical modification of enkephalins while preserving their analgesic efficacy. One example of this is the design of D-Ala-methionine-enkephalin in 1976 by Pert et al. <ref>Pert, C. B., Pert, A., Chang, J. K., & Fong, B. T. (1976). (D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic. Science (New York, N.Y.), 194(4262), 330–332. https://doi.org/10.1126/science.968485</ref>. Kropotova et al. in 2020 have designed different modified enkephalins that are less accessible to endopeptidases <ref>Kropotova, E. S., Ivleva, I. S., Karpenko, M. N., & Mosevitsky, M. I. (2020). Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia. Bioorganic & medicinal chemistry, 28(1), 115184. https://doi.org/10.1016/j.bmc.2019.115184</ref>. Squalene-based nanoparticles have opened exciting perspectives for drug delivery due to their biodegradability and their non-toxicity as Leu-Enkephalin Nanomedicines for pain alleviation. LENK-SQ bioconjugates show exclusively peripheral activity (no BBB penetration) so no CNS addiction and take advantage of the inflammatory process to optimize drug concentrations at the site of injury <ref>Lepetre-Mouelhi S., Feng J., Couvreur P. (2021) New Enkephalin Nanomedicines for Pain Alleviation, Overcoming the Side Effects of Morphine. In: J.M. Abadie M., Pinteala M., Rotaru A. (eds) New Trends in Macromolecular and Supramolecular Chemistry for Biological Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-57456-7_10</ref>.