Hydroxy‐docosahexaenoic acid (DHA‐H) and its immediate metabolite Heneicosapentaenoic acid (HPA) exert neuroprotection and prevent amyloidogenic APP processing

Background DHA-H (Hydroxy-docosahexaenoic acid) is a molecule in development for Alzheimer’s disease (AD) treatment based on the concept of membrane lipid therapy (melitherapy). Once entered cell, metabolized via α-oxidation to fatty acid HPA (Heneicosapentaenoic acid). has been shown reduce amyloidogenic processing Amyloid Precursor Protein (APP), as well having neuroprotective effect cellular models. Although mechanism action not yet fully understood, results obtained excitotoxicity models and profile analysis suggest that could be effector. Methods : APP was assessed cell cultures HEK293 N2a neuroblastoma lines analyzed by western blot. Neuroprotective tested neuron cells differentiated from SH-SY5Y were stimulated with NMDA (N-Methyl-D-Aspartate)/Ca induce excitotoxicity. Lipid samples same cultured addition chloroform/methanol. Fatty acids transformed into methyl esters GC-FID (Gas Chromatography-Flame ionization detector). Results administration decreases levels derivatives processing. showed neuronal model NMDA-induced does significantly alter main but clearly increases cells. Conclusion All these together demonstrate exerts neuroprotection prevents possibly through its metabolic intermediate HPA. Therefore, appears new promising therapy.