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 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 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 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.

Peroxisome Proliferator-Activated Receptor-γ and Its Ligands in the Treatment of Tumors in the Nervous System

2016 ◽  
Vol 11 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Yun Shen ◽  
Yun Lu ◽  
Fang Yu ◽  
Chuntie Zhu ◽  
Hua Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

2020 ◽  
Vol 117 (17) ◽  
pp. 9466-9476 ◽  
Author(s):  
Jolien Wolbert ◽  
Xiaolin Li ◽  
Michael Heming ◽  
Anne K. Mausberg ◽  
Dagmar Akkermann ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nerves ◽  
Myeloid Cells ◽  
Transcriptional Response ◽  
Cell Type ◽  
Glia Cells ◽  
Local Cell ◽  
Infiltrating Lymphocytes

Peripheral nerves contain axons and their enwrapping glia cells named Schwann cells (SCs) that are either myelinating (mySCs) or nonmyelinating (nmSCs). Our understanding of other cells in the peripheral nervous system (PNS) remains limited. Here, we provide an unbiased single cell transcriptomic characterization of the nondiseased rodent PNS. We identified and independently confirmed markers of previously underappreciated nmSCs and nerve-associated fibroblasts. We also found and characterized two distinct populations of nerve-resident homeostatic myeloid cells that transcriptionally differed from central nervous system microglia. In a model of chronic autoimmune neuritis, homeostatic myeloid cells were outnumbered by infiltrating lymphocytes which modulated the local cell–cell interactome and induced a specific transcriptional response in glia cells. This response was partially shared between the peripheral and central nervous system glia, indicating common immunological features across different parts of the nervous system. Our study thus identifies subtypes and cell-type markers of PNS cells and a partially conserved autoimmunity module induced in glia cells.

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