scholarly journals Role of Peroxisome Proliferator-Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-18 ◽  
Author(s):  
Tatiana M. Garcia-Bates ◽  
Geniece M. Lehmann ◽  
Patricia J. Simpson-Haidaris ◽  
Steven H. Bernstein ◽  
Patricia J. Sime ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hematological Malignancies ◽  
Malignant Cell ◽  
Cellular Growth ◽  
Peroxisome Proliferator ◽  
Therapeutic Approaches ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Therapeutic Approaches ◽  
Leukemias And Lymphomas

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifunctional transcription factor with important regulatory roles in inflammation, cellular growth, differentiation, and apoptosis. PPARγis expressed in a variety of immune cells as well as in numerous leukemias and lymphomas. Here, we review recent studies that provide new insights into the mechanisms by which PPARγligands influence hematological malignant cell growth, differentiation, and survival. Understanding the diverse properties of PPARγligands is crucial for the development of new therapeutic approaches for hematological malignancies.

scholarly journals Anticancer Role of PPARγAgonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-36 ◽  
Author(s):  
P. J. Simpson-Haidaris ◽  
S. J. Pollock ◽  
S. Ramon ◽  
N. Guo ◽  
C. F. Woeller ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Radiation Treatment ◽  
Inflammatory Responses ◽  
Combined Therapy ◽  
Chemotherapeutic Agents ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Peroxisome Proliferator Activated Receptor ◽  
Treatment And Prevention

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-γagonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγagonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγagonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγand/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

scholarly journals Role of Peroxisome Proliferator-Activated Receptor-γin Vascular Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kousei Ohshima ◽  
Masaki Mogi ◽  
Masatsugu Horiuchi
Keyword(s):  
Immune Cells ◽  
Adipocyte Differentiation ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Important Regulator ◽  
Artery Disease

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γactivation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γactivation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γinvolvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.

scholarly journals Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

2020 ◽  
Vol 21 (12) ◽  
pp. 4283 ◽  
Author(s):  
Melvin A. Ambele ◽  
Priyanka Dhanraj ◽  
Rachel Giles ◽  
Michael S. Pepper
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Therapeutic Approaches ◽  
Molecular Determinants ◽  
Anatomical Localization ◽  
Two Phases

The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.

scholarly journals Peroxisome Proliferator-Activated Receptor-γIs Critical to Cardiac Fibrosis

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Huang-Jun Liu ◽  
Hai-Han Liao ◽  
Zheng Yang ◽  
Qi-Zhu Tang
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Receptor Superfamily ◽  
Infarction Heart

Peroxisome proliferator-activated receptor-γ(PPARγ) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily, which plays a central role in regulating lipid and glucose metabolism. However, accumulating evidence demonstrates that PPARγagonists have potential to reduce inflammation, influence the balance of immune cells, suppress oxidative stress, and improve endothelial function, which are all involved in the cellular and molecular mechanisms of cardiac fibrosis. Thus, in this review we discuss the role of PPARγin various cardiovascular conditions associated with cardiac fibrosis, including diabetes mellitus, hypertension, myocardial infarction, heart failure, ischemia/reperfusion injury, atrial fibrillation, and several other cardiovascular disease (CVD) conditions, and summarize the developmental status of PPARγagonists for the clinical management of CVD.

scholarly journals The Growing Relevance of Immunoregulation in Pediatric Brain Tumors

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5601
Author(s):  
Viktoria Melcher ◽  
Kornelius Kerl
Keyword(s):  
Brain Tumors ◽  
Immune Cells ◽  
Multimodal Therapy ◽  
Malignant Cell ◽  
Pediatric Brain Tumors ◽  
Therapeutic Approaches ◽  
Aggressive Tumors ◽  
Pediatric Brain ◽  
Heterogeneous Solid

Pediatric brain tumors are genetically heterogeneous solid neoplasms. With a prevailing poor prognosis and widespread resistance to conventional multimodal therapy, these aggressive tumors are the leading cause of childhood cancer-related deaths worldwide. Advancement in molecular research revealed their unique genetic and epigenetic characteristics and paved the way for more defined prognostication and targeted therapeutic approaches. Furthermore, uncovering the intratumoral metrics on a single-cell level placed non-malignant cell populations such as innate immune cells into the context of tumor manifestation and progression. Targeting immune cells in pediatric brain tumors entails unique challenges but promising opportunities to improve outcome. Herein, we outline the current understanding of the role of the immune regulation in pediatric brain tumors.

The emerging role of COX-2, 15-LOX, and PPARγ in metabolic diseases and cancer: An introduction to novel multi-target directed ligands (MTDLs)

2020 ◽  
Vol 27 ◽  
Author(s):  
Rana A. Alaaeddine ◽  
Perihan A. Elzahhar ◽  
Ibrahim AlZaim ◽  
Wassim Abou-Kheir ◽  
Ahmed S.F. Belal ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Targets ◽  
Design And Synthesis ◽  
Early Results ◽  
Cox 2

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

scholarly journals The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 734
Author(s):  
Pietro Antonuccio ◽  
Herbert Ryan Marini ◽  
Antonio Micali ◽  
Carmelo Romeo ◽  
Roberta Granese ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Therapeutic Targets ◽  
Sham Operation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pyrin Domain ◽  
Age Related ◽  
Extracellular Signal ◽  
Morphometric Assessment

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.

scholarly journals From Exercise to Cognitive Performance: Role of Irisin

2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  
Keyword(s):  
The Elderly ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
General Exercise ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain ◽  
The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

scholarly journals The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

2021 ◽  
Author(s):  
Natalia Bryniarska-Kubiak ◽  
Andrzej Kubiak ◽  
Małgorzata Lekka ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Nervous System ◽  
Physical Factors ◽  
Nervous System Diseases ◽  
Therapeutic Approaches ◽  
System Disease ◽  
New Therapeutic Approaches ◽  
The Subject ◽  
Topographical Factors ◽  
New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

scholarly journals The Novel Role of PGC1α in Bone Metabolism

2021 ◽  
Vol 22 (9) ◽  
pp. 4670
Author(s):  
Cinzia Buccoliero ◽  
Manuela Dicarlo ◽  
Patrizia Pignataro ◽  
Francesco Gaccione ◽  
Silvia Colucci ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Osteoblastic Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Sirtuin 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.

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