Background: Alzheimer's disease (AD) is a serious health and economic challenge of the modern age. Current treatments provide only symptomatic relief, making necessary a multitargeted approach against the several pathological processes underlying such disease. In particular, beta-amyloid deposition, tauopathy, astrocyte dysfunction, neuroinflammation and glutamate unbalance recently became promising targets to develop new therapies. In this context, it has been shown that palmitoylethanolamide (PEA) is a multitargeted treatment strategy that provides a novel potential adjunct therapy.
Methods: Here, we tested the effects of a 3-months treatment with ultramicronized PEA (um-PEA), a formulation that improves PEA bioavailability, in young (6-month-old) and adult (12-month-old) 3xTg-AD mice, compared to their age-matched Non-Tg mice. Via a subcutaneous delivery system, the treatment mimicked the clinic use with a chronic daily administration. At the end of the treatments, potential neuropathological mechanisms were assessed by western blot, reverse transcription - polymerase chain reaction (RT-PCR), and immunofluorescence in the hippocampal tissues.
Results: Our finding revealed that um-PEA normalizes astrocytic functionality, rebalances the astrocyte glutamate regulating system, reduces beta-amyloid formation and tau hyperphosphorylation, restrains neuroinflammation and promotes neuronal survival in 3xTg-AD mice. Interestingly, PEA effects where more pronounced in young mice suggesting its potential as an early treatment.
Conclusions: um-PEA is a novel potential treatment whose multitargeted efficacy is powerful especially in early and asymptomatic phases of AD, suggesting its application as a precocious approach. Since PEA is already licenced for use in humans, displaying a high tolerability and safety profile, it would be an ideal candidate for a long-term use lasting several years, as potential AD treatment requires.
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410004222616186240","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410156495"}],"foaf:name":[{"@language":"en","@value":"Bronzuoli Maria Rosanna"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Physiology and Pharmacology, Sapienza University of Rome, Italy"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222616186243","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410156496"}],"foaf:name":[{"@language":"en","@value":"Facchinetti Roberta"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Physiology and Pharmacology, Sapienza University of Rome, Italy"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222616186244","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410156497"}],"foaf:name":[{"@language":"en","@value":"Cassano Tommaso"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222616186242","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410156498"}],"foaf:name":[{"@language":"en","@value":"Steardo Luca"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Physiology and Pharmacology, Sapienza University of Rome, Italy"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222616186241","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410156499"}],"foaf:name":[{"@language":"en","@value":"Scuderi Caterina"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Physiology and Pharmacology, Sapienza University of Rome, Italy"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"24354953"}],"prism:publicationName":[{"@language":"en","@value":"Proceedings for Annual Meeting of The Japanese Pharmacological Society"},{"@language":"ja","@value":"日本薬理学会年会要旨集"}],"dc:publisher":[{"@language":"en","@value":"Japanese Pharmacological Society"},{"@language":"ja","@value":"公益社団法人 日本薬理学会"}],"prism:publicationDate":"2018","prism:volume":"WCP2018","prism:number":"0","prism:startingPage":"PO1-1-65"},"reviewed":"false","jpcoar:conferenceName":"World Congress of Basic and Clinical Pharmacology","jpcoar:conferencePlace":"Kyoto International Conference Center","url":[{"@id":"https://www.jstage.jst.go.jp/article/jpssuppl/WCP2018/0/WCP2018_PO1-1-65/_pdf"}],"availableAt":"2018","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Astrocyte","dc:title":"Astrocyte"},{"@id":"https://cir.nii.ac.jp/all?q=3xTg-AD","dc:title":"3xTg-AD"},{"@id":"https://cir.nii.ac.jp/all?q=Ultramicronized-palmitoylethanolamide","dc:title":"Ultramicronized-palmitoylethanolamide"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2008008666"},{"@type":"CROSSREF","@value":"10.1254/jpssuppl.wcp2018.0_po1-1-65"},{"@type":"CIA","@value":"130007900354"}]}