Peroxisome Proliferator‐Activated Receptor γ is involved in the neuroprotection exerted by 2‐hydroxydocosahexaenoic acid against Alzheimer’s disease

Abstract Background DHA‐H (2‐hydroxy‐docosahexaenoic acid) is a promising therapeutic approach for Alzheimer’s Disease (AD). gives rise to dose‐dependent increased levels of HPA (Heneicosapentaenoic in blood plasma and brain whereas remains virtually absent from the DHA‐H‐treated mice. Oral administration transgenic model AD (5xFAD mice) induces significative cognitive recovery. However, molecular mechanism underlying this neuroprotective effect largely unresolved. Method Screening potential receptors was performed using computational tools. PPARG (Peroxisome Proliferator‐Activated Receptor γ) activity determined by cell‐based assays. Levels proteins involved amyloid production as well synaptic markers were WB and/or ELISA. β‐ γ‐secretase activities measured cell‐free Neuronal density immunohistochemistry. Brain Electrospray Ionization – Mass Spectrometry (ESI‐MS). Result Both are activators PPARG. We have analyzed treatment on amyloidogenic route 5xFAD mice related with activity. observed modulation protein enzymatic β‐amyloid prevention neuron degeneration compared untreated controls. These changes improved scores these Conclusion All results together indicate that must prevent neuronal decline through its immediate metabolite without apparent involvement