LP226A1 in Alzheimer’s disease


LP226A1 is a modified natural fatty acid (DHA derivative) with highly specific incorporation into neurons due to the specific omega-3 transporters present in neuronal membranes. LP226A1 is a potent dose-dependent inhibitor of Tau phosphorylation (both in vitro and in vivo) as determined in differentiated SH-SY5Y cells and in brain samples of transgenic 5xFAD mice with Familiar Alzheimer´s Disease). Treatment of 5xFAD mice with LP226A1 (15 mg/kg daily for 3 months) demonstrated a recovery of cognitive abilities as determined by a computer-assisted-radial maze exercise. This positive behavioural effect correlated with recovery of healthy brain biomarkers and restoration of synaptic protein expression (synaptophysin and SNAP25) in the hippocampus. Concomitant with these effects a loss of the total brain Aβ amyloid load was observed. In addition, in vitro studies demonstrated the capacity of LP226A1 in restoring the viability of SH-SY5Y cells in cell culture intoxicated with Aβamyloid peptide together with significant increases in markers of protective autophagy.


 

Relevant related documents:

::> The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival. Mohaibes RJ et al. Biochim Biophys Acta. 2017 Sep;1859(9 Pt B):1596-1603.

::> Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease. Torres M et al.  Update on Dementia, Dr. Davide Moretti (Ed.), InTech, 2016. DOI: 10.5772/64757.

::> The unfolded protein response in the therapeutic effect of hydroxy-DHA against Alzheimer’s disease. Torres M. et al. Apoptosis. 2015 May;20(5):712-24.

::> Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimers disease. Torres et al. Biochim Biophys Acta. Jun. 2014.

::> Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer’s disease following 2-hydroxy-DHA treatment. Fiol-deRoque et al. Gerontology. Oct. 2013


 

This research is supported by a grant of the Spanish Ministry of Economy and Competitivity (Desarrollo farmacéutico de lípidos de diseño para el tratamiento del ictus y patologías relacionadas (Metabolopatías), ICTUS, Ref: RTC-2015-4094-1)

Proyecto financiado por el Ministerio de Economía y Competitividad y cofinanciado por los Fondos Europeos de Desarrollo Regional (FEDER)

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