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Search Results: 1 - 10 of 303126 matches for " Walter J. Lukiw "
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Variability in micro RNA (miRNA) abundance, speciation and complexity amongst different human populations and potential relevance to Alzheimer's disease (AD)
Walter J. Lukiw
Frontiers in Cellular Neuroscience , 2013, DOI: 10.3389/fncel.2013.00133
Circular RNA (circRNA) in Alzheimer's disease (AD)
Walter J. Lukiw
Frontiers in Genetics , 2013, DOI: 10.3389/fgene.2013.00307
Up-regulation of miRNA-146a in progressive, age-related inflammatory neurodegenerative disorders of the human CNS
Walter J. Lukiw
Frontiers in Neurology , 2014, DOI: 10.3389/fneur.2014.00181
Abstract: Overview The human brain- and retinal-abundant microRNA-146a (miRNA-146a) is an inducible, NF-kB-regulated small non-coding RNA (sncRNA) whose increased expression is associated with pro-inflammatory neurodegeneration in Alzheimer’s disease (AD), age-related macular degeneration (AMD) and prion disease (PrD). In AD, AMD and PrD miRNA-146a modulates the innate-immune response, inflammation and the microglial activation state. This short paper will review and comment on the role of miRNA-146a signaling and how it underlies common molecular-pathogenetic mechanisms in each of these progressive, age-related neurological disorders for which there are currently no effective treatment or cure. microRNA-146a The 22 nucleotide miRNA-146a (miR-146a; hsa-miR-146a-5b; 5’-UGAGAACUGAAUUCCAUGGGUU-3’; 59% A+U; NR_029701), is one of the most intensively studied small non-coding RNAs (sncRNAs) in all of human neurobiology. Encoded from a single locus at chromosome 5q33.3 in humans and at chromosome 11q in mice, miRNA-146a is a rapidly induced, pro-inflammatory miRNA with a relatively short half-life of about 1.5-2 hours in human brain cells and tissues (1-4). This unique member of the miRNA-146 gene family was initially described as being significantly up-regulated after microbial endotoxin, lipopolysaccharide (LPS) or cytokine stimulation of THP1 cells (monocytes; originally derived from an acute monocytic leukemia patient) and under transcriptional control by NF-κB; shortly thereafter this inducible miRNA-146a was found to be up-regulated by metal sulfate-generated reactive oxygen species (ROS), by pro-inflammatory cytokines (such as IL-1β and TNFα) and amyloid peptides (such as Aβ42 peptides) in human primary neuronal-glial (HNG) co-cultures and microglial (HMG) cells (4-7). Each of these independent studies showed the targeting of miRNA-146a to the mRNAs encoding signaling proteins involved in the innate immune and inflammatory response, including complement factor H (CFH) and the interleukin-1 receptor-associated kinase 1 (IRAK-1; the gene partially responsible for IL-1-induced up-regulation of the transcription factor NF-kB; 4-7; see below). Sequencing and promoter analysis of the human miRNA-146a gene subsequently identified three functional and conserved NF-κB binding sites upstream of the miRNA-146a gene, and combined with functionality and NF-kB-inhibition assays was the first NF-κB-regulated miRNA gene identified in the human brain and central nervous system (CNS; 2-4). Interestingly, while miRNA-146a is detectable in mouse and human brain and CNS tissues and
TREM2 signaling, miRNA-34a and the extinction of phagocytosis
Yuhai Zhao,Walter J. Lukiw
Frontiers in Cellular Neuroscience , 2013, DOI: 10.3389/fncel.2013.00131
miRNAs and viroids utilize common strategies in genetic signal transfer
Yuhai Zhao,Surjyadipta Bhattacharjee,Walter J. Lukiw
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00010
Regulating amyloidogenesis through the natural triggering receptor expressed in myeloid/microglial cells 2 (TREM2)
Surjyadipta Bhattacharjee,Yuhai Zhao,Walter J. Lukiw
Frontiers in Cellular Neuroscience , 2014, DOI: 10.3389/fncel.2014.00094
Aluminum-Induced Amyloidogenesis and Impairment in the Clearance of Amyloid Peptides from the Central Nervous System in Alzheimer’s Disease
Yuhai Zhao,Surjyadipta Bhattacharjee,Walter J. Lukiw
Frontiers in Neurology , 2014, DOI: 10.3389/fneur.2014.00167
A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States
Renee Dufault, Walter J Lukiw, Raquel Crider, Roseanne Schnoll, David Wallinga, Richard Deth
Clinical Epigenetics , 2012, DOI: 10.1186/1868-7083-4-6
Abstract: Autism is a developmental disorder defined by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The condition is considered a pervasive developmental disorder (PDD) that appears in the first three years of life and affects brain development impacting social and communication skills. Autism is defined by a common set of behaviors, including, but not limited to, observed deficits in nonverbal and verbal communication, lack of social reciprocity, and failure to develop and maintain appropriate peer relationships [1]. Recent estimates suggest that 31% of children with Autism Spectrum Disorder (ASD) also meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD) and another 24% of children with ASD exhibit sub-threshold clinical symptoms for ADHD [2]. The number of children affected by this debilitating disorder remains unknown. As part of this review, we analyze the current United States (U. S.) Department of Education Special Education data to estimate the increase in autism prevalence from 2005 to 2010.The cause(s) of autism also remain(s) unknown. D'Amelio et al. found paraoxonase-1 (PON1) gene variants associated with autism in subgroups of the U. S. population but not in Italy [3]. They attributed the gene variation to greater household use of organophosphate (OP) pesticides in the U.S. compared to Italy. We think a more plausible explanation may lie in the U. S. food supply. As part of this investigation, we also reviewed and analyzed the U.S. Department of Agriculture (USDA) Food Availability Spreadsheets to identify which foods are most frequently consumed by Americans and of those which most frequently contain OP pesticide residue as reported by the U.S. Pesticide Data Program.During this investigation, we conducted a literature review of all studies published on autism since we published our first Mercury Toxicity Model [4], which explains how mercury exposure, nutritional deficienc
Metal-Sulfate Induced Generation of ROS in Human Brain Cells: Detection Using an Isomeric Mixture of 5- and 6-Carboxy-2′,7′-Dichlorofluorescein Diacetate (Carboxy-DCFDA) as a Cell Permeant Tracer
Aileen I. Pogue,Brandon M. Jones,Surjyadipta Bhattacharjee,Maire E. Percy,Yuhai Zhao,Walter J. Lukiw
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms13089615
Abstract: Evolution of reactive oxygen species (ROS), generated during the patho-physiological stress of nervous tissue, has been implicated in the etiology of several progressive human neurological disorders including Alzheimer’s disease (AD) and amylotrophic lateral sclerosis (ALS). In this brief communication we used mixed isomers of 5-(and-6)-carboxy-2′,7′-dichlorofluorescein diacetate (carboxy-DCFDA; C 25H 14C l2O 9; MW 529.3), a novel fluorescent indicator, to assess ROS generation within human neuronal-glial (HNG) cells in primary co-culture. We introduced pathological stress using the sulfates of 12 environmentally-, industrially- and agriculturally-relevant divalent and trivalent metals including Al, Cd, Cu, Fe, Hg, Ga, Mg, Mn, Ni, Pb, Sn and Zn. In this experimental test system, of all the metal sulfates analyzed, aluminum sulfate showed by far the greatest ability to induce intracellular ROS. These studies indicate the utility of using isomeric mixtures of carboxy-H 2DCFDA diacetates as novel and highly sensitive, long-lasting, cell-permeant, fluorescein-based tracers for quantifying ROS generation in intact, metabolizing human brain cells, and in analyzing the potential epigenetic contribution of different metal sulfates to ROS-generation and ROS-mediated neurological dysfunction.
Docosahexaenoic Acid-Derived Neuroprotectin D1 Induces Neuronal Survival via Secretase- and PPARγ-Mediated Mechanisms in Alzheimer's Disease Models
Yuhai Zhao,Frederic Calon,Carl Julien,Jeremy W. Winkler,Nicos A. Petasis,Walter J. Lukiw,Nicolas G. Bazan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015816
Abstract: Neuroprotectin D1 (NPD1) is a stereoselective mediator derived from the omega-3 essential fatty acid docosahexaenoic acid (DHA) with potent inflammatory resolving and neuroprotective bioactivity. NPD1 reduces Aβ42 peptide release from aging human brain cells and is severely depleted in Alzheimer's disease (AD) brain. Here we further characterize the mechanism of NPD1's neurogenic actions using 3xTg-AD mouse models and human neuronal-glial (HNG) cells in primary culture, either challenged with Aβ42 oligomeric peptide, or transfected with beta amyloid precursor protein (βAPP)sw (Swedish double mutation APP695sw, K595N-M596L). We also show that NPD1 downregulates Aβ42-triggered expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) and of B-94 (a TNF-α-inducible pro-inflammatory element) and apoptosis in HNG cells. Moreover, NPD1 suppresses Aβ42 peptide shedding by down-regulating β-secretase-1 (BACE1) while activating the α-secretase ADAM10 and up-regulating sAPPα, thus shifting the cleavage of βAPP holoenzyme from an amyloidogenic into the non-amyloidogenic pathway. Use of the thiazolidinedione peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone, the irreversible PPARγ antagonist GW9662, and overexpressing PPARγ suggests that the NPD1-mediated down-regulation of BACE1 and Aβ42 peptide release is PPARγ-dependent. In conclusion, NPD1 bioactivity potently down regulates inflammatory signaling, amyloidogenic APP cleavage and apoptosis, underscoring the potential of this lipid mediator to rescue human brain cells in early stages of neurodegenerations.
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