scholarly journals Peroxisome proliferator–activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity

2010 ◽  
Vol 207 (8) ◽  
pp. 1599-1608 ◽  
Author(s):  
Shannon E. Dunn ◽  
Roopa Bhat ◽  
Daniel S. Straus ◽  
Raymond A. Sobel ◽  
Robert Axtell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Autoimmune Inflammation ◽  
Enhanced Expression ◽  
Synthetic Ligand ◽  
Ifn Γ ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator–activated receptors (PPARs; PPAR-α, PPAR-δ, and PPAR-γ) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-δ, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-δ (PPAR-δ−/−) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-γ+IL-17A− and IFN-γ+IL-17A+ CD4+ cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-δ−/− mice occurred as a result of a constellation of immune system aberrations that included higher CD4+ cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-δ in inhibiting the production of IFN-γ and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-δ serves as an important molecular brake for the control of autoimmune inflammation.

scholarly journals Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders

2021 ◽  
Vol 14 (10) ◽  
pp. 1025
Author(s):  
Claudia Sagheddu ◽  
Miriam Melis ◽  
Anna Lisa Muntoni ◽  
Marco Pistis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Evidence ◽  
Peroxisome Proliferator ◽  
Brain Disorders ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
The Central Nervous System ◽  
Peroxisome Proliferator Activated Receptors ◽  
Neuropsychiatric Conditions

Common pathophysiological mechanisms have emerged for different neurological and neuropsychiatric conditions. In particular, mechanisms of oxidative stress, immuno-inflammation, and altered metabolic pathways converge and cause neuronal and non-neuronal maladaptative phenomena, which underlie multifaceted brain disorders. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors modulating, among others, anti-inflammatory and neuroprotective genes in diverse tissues. Both endogenous and synthetic PPAR agonists are approved treatments for metabolic and systemic disorders, such as diabetes, fatty liver disease, and dyslipidemia(s), showing high tolerability and safety profiles. Considering that some PPAR-acting drugs permeate through the blood–brain barrier, the possibility to extend their scope from the periphery to central nervous system has gained interest in recent years. Here, we review preclinical and clinical evidence that PPARs possibly exert a neuroprotective role, thereby providing a rationale for repurposing PPAR-targeting drugs to counteract several diseases affecting the central nervous system.

scholarly journals Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor γ

Brain ◽  
2012 ◽  
Vol 135 (5) ◽  
pp. 1586-1605 ◽  
Author(s):  
Stephanie Hucke ◽  
Juliane Floßdorf ◽  
Berit Grützke ◽  
Ildiko R. Dunay ◽  
Kathrin Frenzel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Myeloid Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Distribution of mRNAs Encoding the Peroxisome Proliferator-Activated Receptor α, β, and γ and the Retinoid X Receptor α, β, and γ in Rat Central Nervous System

2002 ◽  
Vol 70 (4) ◽  
pp. 1366-1375 ◽  
Author(s):  
Tim E. Cullingford ◽  
Kishore Bhakoo ◽  
Stefan Peuchen ◽  
Colin T. Dolphin ◽  
Ritesh Patel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Covering the Role of PGC-1α in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Zuzanna Kuczynska ◽  
Erkan Metin ◽  
Michal Liput ◽  
Leonora Buzanska
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuromuscular Junctions ◽  
Deep Understanding ◽  
Cell Types ◽  
Postnatal Life ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Central Nervous System

The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a well-known transcriptional coactivator involved in mitochondrial biogenesis. PGC-1α is implicated in the pathophysiology of many neurodegenerative disorders; therefore, a deep understanding of its functioning in the central nervous system may lead to the development of new therapeutic strategies. The central nervous system (CNS)-specific isoforms of PGC-1α have been recently identified, and many functions of PGC-1α are assigned to the particular cell types of the central nervous system. In the mice CNS, deficiency of PGC-1α disturbed viability and functioning of interneurons and dopaminergic neurons, followed by alterations in inhibitory signaling and behavioral dysfunction. Furthermore, in the ALS rodent model, PGC-1α protects upper motoneurons from neurodegeneration. PGC-1α is engaged in the generation of neuromuscular junctions by lower motoneurons, protection of photoreceptors, and reduction in oxidative stress in sensory neurons. Furthermore, in the glial cells, PGC-1α is essential for the maturation and proliferation of astrocytes, myelination by oligodendrocytes, and mitophagy and autophagy of microglia. PGC-1α is also necessary for synaptogenesis in the developing brain and the generation and maintenance of synapses in postnatal life. This review provides an outlook of recent studies on the role of PGC-1α in various cells in the central nervous system.

scholarly journals PPARα Modulation-Based Therapy in Central Nervous System Diseases

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1168
Author(s):  
Deokho Lee ◽  
Yohei Tomita ◽  
William Allen ◽  
Kazuo Tsubota ◽  
Kazuno Negishi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Peroxisome Proliferator ◽  
Therapeutic Approaches ◽  
Cns Diseases ◽  
The Central Nervous System ◽  
Peroxisome Proliferator Activated Receptors

The burden of neurodegenerative diseases in the central nervous system (CNS) is increasing globally. There are various risk factors for the development and progression of CNS diseases, such as inflammatory responses and metabolic derangements. Thus, curing CNS diseases requires the modulation of damaging signaling pathways through a multitude of mechanisms. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors (PPARα, PPARβ/δ, and PPARγ), and they work as master sensors and modulators of cellular metabolism. In this regard, PPARs have recently been suggested as promising therapeutic targets for suppressing the development of CNS diseases and their progressions. While the therapeutic role of PPARγ modulation in CNS diseases has been well reviewed, the role of PPARα modulation in these diseases has not been comprehensively summarized. The current review focuses on the therapeutic roles of PPARα modulation in CNS diseases, including those affecting the brain, spinal cord, and eye, with recent advances. Our review will enable more comprehensive therapeutic approaches to modulate PPARα for the prevention of and protection from various CNS diseases.

Bisphenol A diglycidyl ether induces apoptosis in tumour cells independently of peroxisome proliferator-activated receptor-γ, in caspase-dependent and -independent manners

2002 ◽  
Vol 362 (3) ◽  
pp. 573-578 ◽  
Author(s):  
Sebastian FEHLBERG ◽  
Stefan TRAUTWEIN ◽  
Alexandra GÖKE ◽  
Rüdiger GÖKE
Keyword(s):  
Bisphenol A ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Cytotoxic Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Bisphenol A Diglycidyl Ether ◽  
Peroxisome Proliferator Activated Receptors ◽  
Necrosis Factor

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors which are involved in many biological processes, such as regulation of cell differentiation, lipid metabolism, inflammation and cell death. PPARs consist of three families, PPAR-α, PPAR-δ and PPAR-γ. Bisphenol A diglycidyl ether (BADGE) has been described as a pure antagonist of PPAR-γ. However, recent data also revealed PPAR-γ-agonistic activities of BADGE. Here we show that BADGE kills transformed cells by apoptosis and promotes the cytotoxic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and indomethacin. The cytotoxic effect of BADGE does not require PPAR-γ expression and is mediated in caspase-dependent and caspase-independent manners.

Peroxisome proliferator-activated receptor-γ and its ligands attenuate biologic functions of human natural killer cells

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3276-3284 ◽  
Author(s):  
Xia Zhang ◽  
Maria Cecilia Rodriguez-Galán ◽  
Jeff J. Subleski ◽  
John R. Ortaldo ◽  
Deborah L. Hodge ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Interferon Γ ◽  
Cytolytic Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Ppar Γ ◽  
Ifn Γ

Abstract Interferon-γ (IFN-γ) production and cytolytic activity are 2 major biologic functions of natural killer (NK) cells that are important for innate immunity. We demonstrate here that these functions are compromised in human NK cells treated with peroxisome proliferator-activated-γ (PPAR-γ) ligands via both PPAR-γ-dependent and -independent pathways due to variation in PPAR-γ expression. In PPAR-γ-null NK cells, 15-deoxy-Δ12,14 prostaglandin J2 (15d-PGJ2), a natural PPAR-γ ligand, reduces IFN-γ production that can be reversed by MG132 and/or chloroquine, and it inhibits cytolytic activity of NK cells through reduction of both conjugate formation and CD69 expression. In PPARγ-positive NK cells, PPAR-γ activation by 15d-PGJ2 and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-γ. Overexpression of PPAR-γ in PPAR-γ-null NK cells reduces IFN-γ gene expression. However, PPAR-γ expression and activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ2 but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44 expression is not affected. These results reveal novel pathways regulating NK cell biologic functions and provide a basis for the design of therapeutic agents that can regulate the function of NK cells within the innate immune response. (Blood. 2004;104:3276-3284)

Expression of Peroxisome Proliferator-activated Receptors α, β, γ, and H- and L-Prostaglandin D Synthase During Osteoarthritis in the Spontaneous Hartley Guinea Pig and Experimental Dog Models

2013 ◽  
Vol 40 (6) ◽  
pp. 877-890 ◽  
Author(s):  
Sarah-Salwa Nebbaki ◽  
Fatima Ezzahra El Mansouri ◽  
Hassan Afif ◽  
Mohit Kapoor ◽  
Mohamed Benderdour ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Cruciate Ligament ◽  
Research Society ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Prostaglandin D Synthase ◽  
Enhanced Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Spearman Test

Objective.To investigate the expression of peroxisome proliferator-activated receptors (PPAR) α, β, and γ, and hematopoietic and lipocalin-type prostaglandin D synthase (H- and L-PGDS) over the course of osteoarthritis (OA) in the spontaneous Hartley guinea pig and the anterior cruciate ligament transection dog models.Methods.Guinea pigs were sacrificed at 2 (control group), 4, 8, and 12 months of age (n = 5 per group). Non-operated (control) and operated dogs were sacrificed at 4, 8, and 12 weeks postsurgery. Cartilage was evaluated histologically using the Osteoarthritis Research Society International (OARSI) guidelines. The expression of PPAR-α, β, γ, and H- and L-PGDS was evaluated by real-time PCR and immunohistochemistry. The nonparametric Spearman test was used for correlation analysis.Results.PPAR-α, β, and γ were detected in medial tibial plateau from control animals in both the spontaneous and surgical models. Levels of PPAR-α and β did not change over the course of OA, whereas PPAR-γ levels decreased during progression of disease. We also observed that the expression of H-PGDS remained unchanged, whereas L-PGDS increased over the course of OA. PPAR-γ levels correlated negatively, whereas L-PGDS levels correlated positively, with the histological score of OA.Conclusion.The level of PPAR-γ decreased, whereas level of L-PGDS increased during the progression of OA. These data suggest that reduced expression of PPAR-γ may contribute to the pathogenesis of OA, whereas enhanced expression of L-PGDS may be part of a reparative process.

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