ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
This article is part of the Research TopicImmune Responses in Neurodegeneration: Opportunities for Targeted InterventionsView all 3 articles
The immunomodulating effect of palmitoylethanolamide on human myeloid dendritic cells and its possible impact on Alzheimer's disease
Provisionally accepted
Iliana Piccolino1
Filomena Iannuzzi1
Ludovica Lionetti1
Benedetta Mazzonello1
Fabrizio Piras2
Nerisa Banaj2
Valeria Barreca3
Valentina Arezzini2
Paola Bossù1*- 1Experimental Neuropsychobiology Lab, Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation (IRCCS), Rome, Italy
- 2Neuropsychiatry Lab, Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation (IRCCS), Rome, Italy
- 3Istituto Superiore di Sanita, Rome, Italy
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Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that has emerged as a promising therapeutic candidate for neurodegenerative disorders, particularly Alzheimer's disease (AD). Recognized for its inherent anti-inflammatory, analgesic, immunomodulatory, and neuroprotective properties, PEA possesses a good potential as a novel treatment addressing neuroinflammation associated with neurodegeneration, even though its precise mechanisms of action remain to be fully understood. Dendritic cells (DCs) are specialized migratory innate immune cells that play a crucial role in initiating and regulating immune responses and inflammation in both the body and the brain. In AD, DCs display a dysfunctional, pro-inflammatory profile, suggesting their involvement in disease pathology and progression. To explore the therapeutic potential of PEA, this study investigated its effects in vitro on human monocyte-derived DCs under both normal and AD-like conditions. The results show that PEA exerts significant immunomodulatory effects, promoting the maturation of DCs in both healthy and disease states. Notably, PEA treatment appears to correct the dysregulated state of DCs observed in AD conditions. This study reveals a novel mechanism by which PEA modulates immune activity through its action on DCs. By restoring normal DC function in neurodegenerative settings, PEA may help reduce inflammation, highlighting its potential as a therapeutic agent for Alzheimer's disease.
Keywords: Palmitoylethanolamide (PEA), Monocyte-derived dendritic cells (MDDCs), Immunomodulation, DC immunobiology, Alzheimer's disease, Inflammation, Neurodegenerative Diseases
Received: 11 Jul 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Piccolino, Iannuzzi, Lionetti, Mazzonello, Piras, Banaj, Barreca, Arezzini and Bossù. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Paola Bossù
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