Abstract
Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release of proinflammatory and pro-oxidant mediators. Activated glial cells may release also pro-angiogenic molecules. The role of angiogenesis in AD is still controversial: although angiogenesis brings oxygen and nutrients to injured tissue, it may also exacerbate reactive gliosis. Moreover, by altering blood-brain barrier permeability pro-angiogenic mediators promote passage of inflammatory/immune-competent cells into the brain, thereby exacerbating gliosis. The release of proangiogenic factors during astrogliosis may thus be a key-step in controlling AD progression. The endogenous fatty acid amide, palmitoylethanolamide (PEA), is a pleiotropic mediator exerting anti-inflammatory, antinociceptive and antiangiogenic effects in several in vitro and in vivo models of chronic-degenerative disease. In this study, we investigated the effects of PEA in AD angiogenesis and neuroinflammation by using conditioned medium from untreated and Aβ-treated C6 rat astroglioma cells and HUVEC human endothelial cells. PEA (10-8-10-6 M) concentration-dependently reduced expression of pro-inflammatory and pro-angiogenic markers in Aβ (1 μg/mL)-stimulated C6 cells. Moreover, culture medium from PEA-treated C6 cells reduced HUVEC cell proliferation as compared to cells treated with conditioned medium from Aβ-treated C6 cells. Immunocytochemical analysis revealed that PEA treatment inhibited nuclear levels of mitogen-activated protein kinase 1 (the main pro-angiogenic pathway) and cytoplasmic vascular endothelial growth factor in HUVEC cells receiving C6 conditioned medium. Finally, the peroxisome proliferator-activated receptor alpha inhibitor GW6471, added to Aβ-treated C6 cells blocked all PEA effects in this model, suggesting that PEA acts through a proliferator-activated receptor alpha-dependent mechanism on astroglial cells. Collectively, these data support the potential therapeutic utility of PEA in AD.
Keywords: Angiogenesis, astrogliosis, palmitoylethanolamide.
CNS & Neurological Disorders - Drug Targets
Title:Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro
Volume: 14 Issue: 7
Author(s): Mariateresa Cipriano, Giueseppe Esposito, Luana Negro, Elena Capoccia, Giovanni Sarnelli, Caterina Scuderi, Daniele De Filippis, Luca Steardo and Teresa Iuvone
Affiliation:
Keywords: Angiogenesis, astrogliosis, palmitoylethanolamide.
Abstract: Aβ-induced astrogliosis can worsen the eziopathogenesis of Alzheimer disease (AD) by the release of proinflammatory and pro-oxidant mediators. Activated glial cells may release also pro-angiogenic molecules. The role of angiogenesis in AD is still controversial: although angiogenesis brings oxygen and nutrients to injured tissue, it may also exacerbate reactive gliosis. Moreover, by altering blood-brain barrier permeability pro-angiogenic mediators promote passage of inflammatory/immune-competent cells into the brain, thereby exacerbating gliosis. The release of proangiogenic factors during astrogliosis may thus be a key-step in controlling AD progression. The endogenous fatty acid amide, palmitoylethanolamide (PEA), is a pleiotropic mediator exerting anti-inflammatory, antinociceptive and antiangiogenic effects in several in vitro and in vivo models of chronic-degenerative disease. In this study, we investigated the effects of PEA in AD angiogenesis and neuroinflammation by using conditioned medium from untreated and Aβ-treated C6 rat astroglioma cells and HUVEC human endothelial cells. PEA (10-8-10-6 M) concentration-dependently reduced expression of pro-inflammatory and pro-angiogenic markers in Aβ (1 μg/mL)-stimulated C6 cells. Moreover, culture medium from PEA-treated C6 cells reduced HUVEC cell proliferation as compared to cells treated with conditioned medium from Aβ-treated C6 cells. Immunocytochemical analysis revealed that PEA treatment inhibited nuclear levels of mitogen-activated protein kinase 1 (the main pro-angiogenic pathway) and cytoplasmic vascular endothelial growth factor in HUVEC cells receiving C6 conditioned medium. Finally, the peroxisome proliferator-activated receptor alpha inhibitor GW6471, added to Aβ-treated C6 cells blocked all PEA effects in this model, suggesting that PEA acts through a proliferator-activated receptor alpha-dependent mechanism on astroglial cells. Collectively, these data support the potential therapeutic utility of PEA in AD.
Export Options
About this article
Cite this article as:
Cipriano Mariateresa, Esposito Giueseppe, Negro Luana, Capoccia Elena, Sarnelli Giovanni, Scuderi Caterina, Filippis De Daniele, Steardo Luca and Iuvone Teresa, Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro, CNS & Neurological Disorders - Drug Targets 2015; 14 (7) . https://dx.doi.org/10.2174/1871527314666150317224155
DOI https://dx.doi.org/10.2174/1871527314666150317224155 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Heart and Brain Axis Targets in CNS Neurological Disorders
Recently there has been a surge of interest in delving deeper into the complex interplay between the heart and brain. This fascination stems from a growing recognition of the profound influence each organ holds over the other, particularly in the realm of central nervous system (CNS) neurological disorders. The purpose ...read more
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Cytokines Play a Key Role in Communication between Mesenchymal Stem Cells and Brain Cancer Cells
Protein & Peptide Letters Synthesis of Silica Based Nanoparticles Against the Proliferation of Human Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Anti-miRNA-23a Oligonucleotide Suppresses Glioma Cells Growth by Targeting Apoptotic Protease Activating Factor-1
Current Pharmaceutical Design Summary of Information on the Effects of Ionizing and Non-ionizing Radiation on Cytochrome P450 and Other Drug Metabolizing Enzymes and Transporters
Current Drug Metabolism Clonetics
Current Drug Metabolism Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Current Pharmaceutical Design Dendritoma Vaccine for Cancer: A Hopeful Approach
Current Cancer Therapy Reviews Combination Therapy of Chemotherapy or Radiotherapy and the Neurokinin-1 Receptor Antagonist Aprepitant: A New Antitumor Strategy?
Current Medicinal Chemistry Matrix Metalloproteinases: Drug Targets for Myocardial Infarction
Current Drug Targets Multiple Protective Functions of Sigma1 Receptor
Current Protein & Peptide Science Synthesis and Biological Evaluation of Triazole-Vanillin Molecular Hybrids as Anti-Cancer Agents
Current Bioactive Compounds Application of dsRNA in Cancer Immunotherapy: Current Status and Future Trends
Anti-Cancer Agents in Medicinal Chemistry Perspectives/Opinion: ADVANCED MEDICAL IMAGING IN THE ERA OF PERSONALIZED OR PRECISION MEDICINE
Current Medical Imaging Production of Retroviral Vectors: Review
Current Gene Therapy TGF-β Pathway as a Therapeutic Target in Bone Metastases
Current Pharmaceutical Design Current Experimental, Bioinformatic and Statistical Methods used in NMR Based Metabolomics
Current Metabolomics Preparation and <I>In Vitro/Vivo</I> Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery
Current Drug Delivery Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy
Current Gene Therapy Immunophilin Dysfunction and Neuropathology
Current Medicinal Chemistry Is Fibroblast Growth Factor Receptor 4 a Suitable Target of Cancer Therapy?
Current Pharmaceutical Design