protein-kinase-c-delta-inhibitor-peptide-formulation-using-gold

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles

Protein kinase C-delta inhibitor (PKC&#948;i) is a promising drug to prevent ischemia-reperfusion-induced organ injury. It is usually conjugated to a ...

scoring-central-nervous-system-inflammation-demyelination-axon-injury

Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a common immune-based model of multiple sclerosis (MS). This disease can be induced in rodents by ...

University Health Network

Keenan Research Centre for Biomedical Science of St. Michael’s Hospital

Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor that functions to maintain metabolic homeostasis, regulate cell growth, and limit the development of excessive inflammation during immune responses. Previously, we reported that PPAR-δ-deficient mice develop a more severe clinical course of experimental autoimmune encephalomyelitis (EAE); however, it was difficult to delineate the role that microglia played in this disease phenotype since PPAR-δ-deficient mice exhibited a number of immune defects that enhanced CNS inflammation upstream of microglia activation. Here, we specifically investigated the role of PPAR-δ in microglia during EAE by using mice where excision of a floxed  allele was driven by expression of a tamoxifen (TAM)-inducible CX3C chemokine receptor 1 promoter-Cre recombinase transgene (: ). We observed that by 30 days of TAM treatment, :  mice exhibited Cre-mediated deletion primarily in microglia and this was accompanied by efficient knockdown of  expression in these cells. Upon induction of EAE, TAM-treated :  mice presented with an exacerbated course of disease compared to TAM-treated  controls. Histopathological and magnetic resonance (MR) studies on the spinal cord and brains of EAE mice revealed increased Iba-1 immunoreactivity, axonal injury and CNS tissue loss in the TAM-treated :  group compared to controls. In early EAE, a time when clinical scores and the infiltration of CD45 leukocytes was equivalent between :  and  mice, -deficient microglia exhibited a more reactive phenotype as evidenced by a shorter maximum process length and lower expression of genes associated with a homeostatic microglia gene signature. In addition, -deficient microglia exhibited increased expression of genes associated with reactive oxygen species generation, phagocytosis and lipid clearance, M2-activation, and promotion of inflammation. Our results therefore suggest that PPAR-δ has an important role in microglia in limiting bystander tissue damage during neuroinflammation.

Peroxisome Proliferator-Activated Receptor-δ Deficiency in Microglia Results in Exacerbated Axonal Injury and Tissue Loss in Experimental Autoimmune Encephalomyelitis.

Annette Gower

Latner Thoracic Surgery Research Laboratories,
Toronto General Hospital Research Institute,
Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute

University Health Network

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles

Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis

Annette Gower

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Latner Thoracic Surgery Research Laboratories,Toronto General Hospital Research Institute,Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute

University Health Network

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles

Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis

Latner Thoracic Surgery Research Laboratories,
Toronto General Hospital Research Institute,
Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute