Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Primary Astrocytes: Involvement of Peroxisome‐Proliferator Activated Receptor‐α

  title={Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Primary Astrocytes: Involvement of Peroxisome‐Proliferator Activated Receptor‐$\alpha$},
  author={Giuseppina Mattace Raso and Emanuela Esposito and Sergio Vitiello and Anna Iacono and Anna Santoro and Giuseppe D'Agostino and Oscar Sasso and Roberto Russo and P. V. Piazza and Antonio Calignano and Rosaria Meli},
  journal={Journal of Neuroendocrinology},
Palmitoylethanolamide (PEA) regulates many pathophysiological processes in the central nervous system, including pain perception, convulsions and neurotoxicity, and increasing evidence points to its neuroprotective action. In the present study, we report that PEA, acting as a ligand of peroxisome‐proliferator activated receptor (PPAR)‐α, might regulate neurosteroidogenesis in astrocytes, which, similar to other glial cells and neurones, have the enzymatic machinery for neurosteroid de novo… 
TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis.
  • A. Santoro, G. Mattace Raso, R. Meli
  • Biology
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2016
Glia and Mast Cells as Targets for Palmitoylethanolamide, an Anti-inflammatory and Neuroprotective Lipid Mediator
A proposed mast cell–glia communication may open new perspectives for designing therapies to target neuroinflammation by differentially modulating activation of non-neuronal cells normally controlling neuronal sensitization—both peripherally and centrally.
Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα
This review mobilizes a considerable number of findings that discuss miscellaneous axes, covering the detailed expression pattern of PPARα in species and tissues, the lessons from several PPAR α KO mouse models and the modulation ofPPARα function by dietary micronutrients.
Macrophage-derived lipid agonists of PPAR-α as intrinsic controllers of inflammation
Recent findings on the contribution of the FAE-PPAR-α signaling complex in inflammation, and on NAAA inhibition as a novel mechanistic approach to treat chronic inflammatory disorders are summarized.
Allopregnanolone attenuates Aβ25-35-induced neurotoxicity in PC12 cells by reducing oxidative stress.
  • X. Qian, H. Cao, Jun Li
  • Biology, Chemistry
    International journal of clinical and experimental medicine
  • 2015
It is demonstrated that Allopregnano-lone (APα), a neurosteroid derive from neuroactive progesterone, exerts a protective effect against Aβ25-35-induced neurotoxicity in PC12 cells.
Neuroprotective Activities of Palmitoylethanolamide in an Animal Model of Parkinson's Disease
Chronic treatment with palmitoylethanolamide (PEA) protects against MPTP-induced neurotoxicity and the ensuing functional deficits even when administered once the insult has been initiated, and chronic PEA reversedMPTP-associated motor deficits.


Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-α Agonist, Modulates Carrageenan-Induced Paw Edema in Mice
Central PEA administration significantly reduced the expression of the proinflammatory enzymes cyclooxygenase-2 and inducible nitric-oxide synthase, and it significantly restored carrageenan-induced PPAR-α reduction in the spinal cord, confirming the involvement of this transcriptional factor in the control of peripheral inflammation.
Anti‐apoptotic effects of allopregnanolone on P19 neurons
The results suggest that neurosteroids, interfering with the mitochondrial apoptotic pathway, are able to act as survival factors in neuronal cells, while they contribute to GABAA receptor plasticity modulating the expression of its subunits.
The neuroprotective properties of palmitoylethanolamine against oxidative stress in a neuronal cell line
EA protects HT22 cells from oxidative stress and alters the localization and expression levels of kinases known to be involved in neuroprotection by a novel mechanism, identifying PEA as a neuroprotectant with potential as a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
Findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPar-α.
The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons.
  • S. Skaper, A. Buriani, A. Leon
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
The results suggest that non-CB1 cannabinoid receptors control, upon agonist binding, the downstream consequences of an excitotoxic stimulus and activation of such receptors may serve to downmodulate deleterious cellular processes following pathological events or noxious stimuli in both the nervous and immune systems.
Steroidogenic Acute Regulatory Protein Expression and Pregnenolone Synthesis in Rat Astrocyte Cultures
Novel results indicate that cyclic AMP signalling can regulate StAR expression and pregnenolone production in brain astrocytes, and provide additional insight into the role of StAR in neurosteroidogenesis.
Palmitoylethanolamide Increases after Focal Cerebral Ischemia and Potentiates Microglial Cell Motility
The results show that PEA and AEA increase after FCI and synergistically enhance microglial cell motility, and evidence is provided that P EA acts through Gi/o-coupled receptors, which are pharmacologically distinct from CB1 and CB2 cannabinoid receptors.
Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis
It is demonstrated that 5α-R type I and 3α-HSD colocalize in cortical, hippocampal, and olfactory bulb glutamatergic principal neurons and in some output neurons of the amygdala and thalamus, and data suggest that ALLO and THDOC modulate GABA action at GABAA receptors, either with an autocrine or a paracrine mechanism or by reaching GabAA receptor intracellular sites through lateral membrane diffusion.