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Cell Death Dis. 2014 Sep 11;5:e1419. doi: 10.1038/cddis.2014.376.

Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer's disease.

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Department of Physiology and Pharmacology 'Vittorio Erspamer'-SAPIENZA University of Rome, P.le A. Moro, Rome 5-00185, Italy.
Laboratory of the Biology of Addictive Diseases-The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Department of Psychiatry-University of Naples SUN, Largo Madonna delle Grazie, Naples 1-80138, Italy.
Department of Anatomy, Histology, Forensic Medicine and Orthopedics-SAPIENZA University of Rome, Via A. Borelli 50, Rome 00161, Italy.


Given the complex heterogeneity of pathological changes occurring in Alzheimer's disease (AD), any therapeutic effort absolutely requires a multi-targeted approach, because attempts addressing only a single event may result ineffective. Palmitoylethanolamide (PEA), a naturally occurring lipid amide between palmitic acid and ethanolamine, seems to be a compound able to fulfill the criteria of a multi-factorial therapeutic approach. Here, we describe the anti-inflammatory and neuroprotective activities of systemic administration of PEA in adult male rats given intrahippocampal injection of beta amyloid 1-42 (Aβ 1-42). Moreover, to investigate the molecular mechanisms responsible for the effects induced by PEA, we co-administered PEA with the GW6471, an antagonist of peroxisome proliferator-activated receptor-α (PPAR-α). We found that Aβ 1-42 infusion results in severe changes of biochemical markers related to reactive gliosis, amyloidogenesis, and tau protein hyperphosphorylation. Interestingly, PEA was able to restore the Aβ 1-42-induced alterations through PPAR-α involvement. In addition, results from the Morris water maze task highlighted a mild cognitive deficit during the reversal learning phase of the behavioral study. Similarly to the biochemical data, also mnestic deficits were reduced by PEA treatment. These data disclose novel findings about the therapeutic potential of PEA, and suggest novel strategies that hopefully could have the potential not just to alleviate the symptoms but also to modify disease progression.

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