Characterization of an NF-κB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells

Pogue, Aileen I.; Li, Yuan Yuan; Cui, Jian; Zhao, Yuhai; Kruck, Theo P.A.; Percy, Maire E.; Tarr, Matthew A.; Lukiw, Walter J.

doi:10.1016/j.jinorgbio.2009.05.012

Cited by 126 publications

(176 citation statements)

References 13 publications

(46 reference statements)

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“…Aluminum is expected to induce biosemiotic entropy through multiple pathways [22,63,64]. Its +3 charge and highly kosmotropic properties make it extremely destructive in water-based biological systems.…”

Section: Mechanisms Of Aluminum and Mercury Toxicitymentioning

confidence: 99%

“…Exposure of human neuronal cells to a low concentration (100 nM) of aluminum sulfate induces a response that emulates the gene expression changes associated with Alzheimer's disease [67]. Recently, a group of researchers investigated the effect of aluminum sulfate on an in vitro culture of human neural cells [63], which was directly compared to the effect of magnesium-, iron-and zinc sulfate. They confirmed that, by contrast with the other salts, aluminum sulfate had an unusual and significant ability to induce NF-κB signaling and subsequent reactive oxygen species (ROS), mediated by down-regulation of the important inflammation inhibitor, complement factor H (CFH).…”

Section: Mechanisms Of Aluminum and Mercury Toxicitymentioning

confidence: 99%

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Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

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Section: Mechanisms Of Aluminum and Mercury Toxicitymentioning

confidence: 99%

Section: Mechanisms Of Aluminum and Mercury Toxicitymentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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“…Age-matched control and 5xFAD brain and/or retina at 0, 1.5, 3 and 5 months were analyzed for Aβ40 and Aβ42 peptide and COX-2 and CRP protein levels using ELISA and Western analysis [3,[5][6][7][8]. Further details on the quality control for these 5xFAD brain and retinal samples, sample handling and analysis have been recently published [3,[18][19][20][21]. Total brain and retinal RNA and protein were isolated using TRIzol reagent; RNA was archived for further analysis (Invitrogen, Carlsbad, CA, USA).…”

Section: Reagents Brain and Retinal Tissues Protein Extraction Andmentioning

confidence: 99%

“…Total brain and retinal RNA and protein were isolated using TRIzol reagent; RNA was archived for further analysis (Invitrogen, Carlsbad, CA, USA). Protein concentrations were determined using a dotMETRIC microassay as previously described (sensitivity 0.3 ng protein/ml; Chemicon-Millipore, Billerica, Massachusetts, USA) [18][19][20][21][22][23][24][25][26].…”

Section: Reagents Brain and Retinal Tissues Protein Extraction Andmentioning

confidence: 99%

“…Western gels and enzyme-linked immunoabsorbent assay (ELISA) were performed for quantification of Aβ40 and Aβ42 peptides and total Aβ40 + Aβ42 peptide load in control and transgenic mouse brain and retina as previously described [18][19][20][24][25][26]. Western immunoblots were performed using murine-and/or human-specific primary antibodies directed against Aβ40 or Aβ42 peptide (BDI350; ab20068 or ab10148; Abcam, Cambridge, MA, USA), the control protein marker β-actin (3598-100; Sigma-Aldrich Chemical Company, St. Louis, Missouri, USA), CRP (N-14; sc-18304), CRP (H-90; sc-30047) and/or CRP (C-13; sc-18306), COX-1 (AS70; sc-52757 and/or 41272; sc-70878), COX-2 (H3; sc-376861 and/or H-62; sc-7951; Santa Cruz Biotechnologies, CA, USA) using methods previously described by our group [18][19][20][21][22][23][24][25][26][27].…”

Section: Elisa and Western Analysismentioning

confidence: 99%

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P3‐117: Progressive Inflammatory Pathology in the Retina of Aluminum‐Fed 5XFAD Transgenic Mice

Pogue¹,

Lukiw

Percy

et al. 2016

Alzheimer's & Dementia

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At least 57 murine transgenic models for Alzheimer's disease (Tg-AD) have been developed to overexpress the 42 amino acid amyloid-beta (Aβ42) peptide in the central nervous system (CNS). These 'humanized murine Tg-AD models' have greatly expanded our understanding of the contribution of Aβ42 peptide-mediated pro-inflammatory neuropathology to the AD process. A number of independent laboratories using different amyloid-overexpressing Tg-AD models have shown that supplementation of murine Tg-AD diets and/or drinking water with aluminum significantly enhances Aβ42 peptide-mediated inflammatory pathology and AD-type cognitive change compared to animals receiving control diets. In humans AD-type pathology appears to originate in the limbic system and progressively spreads into primary processing and sensory regions such as the retina. In these studies, for the first time, we assess the propagation of Aβ42 and inflammatory signals into the retina of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum. The two most interesting findings were (1) that similar to other Tg-AD models, there was a significantly accelerated development of Aβ42 and inflammatory pathology in 5xFAD Tg-AD mice fed aluminum; and (2) in aluminumsupplemented animals, markers for inflammatory pathology appeared in both the brain and the retina as evidenced by an evolving presence of Aβ42 peptides, and accompanied by inflammatory markers -cyclooxygenase-2 (COX-2) and C-reactive protein (CRP). The results indicate that in the 5xFAD Tg-AD model aluminum not only enhances an Aβ42-mediated inflammatory degeneration of the brain but also appears to induce AD-type pathology in an anatomically-linked primary sensory area that involves vision.

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Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders

Gupta

Verma

Mantri

et al. 2015

Drug Development Research

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Preclinical Research microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that are key regulators of gene expression. They act on wide range of targets by binding to mRNA via imperfect complementarity at 3' UTR. Evidence suggests that miRNAs regulate many biological processes including neuronal development, differentiation, and disease. Altered expression of several miRNAs has been reported in many neurodegenerative disorders (NDDs). Many miRNAs are altered in these diseases, but miRNA 15, miRNA 21, and miRNA 146a have been shown to play critical role in many neurodegenerative conditions. As these miRNAs regulate many genes, miRNA targeted approaches would allow concurrently targeting of multiple effectors of pathways that regulate disease progression. In this review, we describe the role of miRNAs in various NDDs and their potential as therapeutic tools in prevention and treatment of neurological conditions.

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Characterization of an NF-κB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells

Cited by 126 publications

References 13 publications

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

P3‐117: Progressive Inflammatory Pathology in the Retina of Aluminum‐Fed 5XFAD Transgenic Mice

Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders

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