Rosiglitazone acts as a neuroprotectant in retinal cells via up‐regulation of sestrin‐1 and SOD‐2

Doonan, Francesca; Wallace, Deborah; O’Driscoll, Carolyn; Cotter, Thomas G.

doi:10.1111/j.1471-4159.2009.05995.x

Cited by 36 publications

(38 citation statements)

References 39 publications

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“…Among the top predictions, retinal disorders and glaucoma are also listed. It is reported that rosiglitazone is a potential neuroprotectant for retinal cells and may increase the retinal cell survival40. It may also delay the onset of proliferative diabetic retinopathy41.…”

Section: Resultsmentioning

confidence: 99%

DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

Luo

Zhang

Cao

et al. 2016

Sci Rep

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The cost of developing a new drug has increased sharply over the past years. To ensure a reasonable return-on-investment, it is useful for drug discovery researchers in both industry and academia to identify all the possible indications for early pipeline molecules. For the first time, we propose the term computational “drug candidate positioning” or “drug positioning”, to describe the above process. It is distinct from drug repositioning, which identifies new uses for existing drugs and maximizes their value. Since many therapeutic effects are mediated by unexpected drug-protein interactions, it is reasonable to analyze the chemical-protein interactome (CPI) profiles to predict indications. Here we introduce the server DPDR-CPI, which can make real-time predictions based only on the structure of the small molecule. When a user submits a molecule, the server will dock it across 611 human proteins, generating a CPI profile of features that can be used for predictions. It can suggest the likelihood of relevance of the input molecule towards ~1,000 human diseases with top predictions listed. DPDR-CPI achieved an overall AUROC of 0.78 during 10-fold cross-validations and AUROC of 0.76 for the independent validation. The server is freely accessible via http://cpi.bio-x.cn/dpdr/.

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Section: Resultsmentioning

confidence: 99%

DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

Luo

Zhang

Cao

et al. 2016

Sci Rep

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“…Thus, rosiglitazone-PPAR-γ protects against hypoxia-and oxidant-induced apoptosis by attenuating reactive oxygen species (ROS) production and thereby controls premitochondrial apoptotic targets [11]. Furthermore, PPAR-γ agonists mediate the transcription of superoxide dismutase (SOD) and catalase genes, PPRE sites were found at the promoter region of these two genes, and their upregulation is reversed by the PPAR-γ antagonist GW9662, while PPAR-γ agonists downregulate the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [56][57][58][59]. SOD and catalase are known free radical scavengers, while NADPH oxidase is a ROS generator.…”

Section: Ppar-γ and Post-ischemic Apoptosismentioning

confidence: 98%

Anti-apoptotic Actions of PPAR-γ Against Ischemic Stroke

Fong¹,

Tsai²,

Chen³

et al. 2010

Mol Neurobiol

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Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-gamma can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-gamma against cerebral ischemia. PPAR-gamma, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt. The preserved Akt phosphorylated Bad. Meanwhile, PPAR-gamma also promotes the transcription of 14-3-3epsilon. Elevated 14-3-3epsilon binds and sequesters p-Bad and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl-2. This review further supports the notion that PPAR-gamma may serve as a potential therapeutic target for treating ischemic stroke.

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“…Troglitazone treatment, another antidiabetic and anti-inflammatory drug, results in decreased expression of HNF4A and SOD2 mRNAs in cellular models (Lauer, et al, 2009,Ruan, et al, 2003. In addition, gliclazide treatment, an oral sulfonylurea hypoglycemic agent, results in decreased protein expression of SOD2 (Onozato, et al, 2004), and rosiglitazone, an insulin sensitizer, increased SOD2 protein expression in retinal cells from mice (Doonan, et al, 2009). Based on these observations, expression of HNF4A and SOD2 in blood may be useful to evaluate the therapeutic effect of anti-diabetic drugs in PD patients.…”

Section: Discussionmentioning

confidence: 99%

Splice Variant Biomarkers for Parkinson's Disease

Potashkin¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEMay PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERRosalind Franklin U. Medicine & Science 3333 Green Bay Rd. North Chicago, IL 60064-3037 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTRecently we identified splice variants in whole blood than can distinguish early stage Parkinson's disease (PD) patients from healthy and neurodegenerative controls. The proposed studies will test the hypothesis that the biomarkers will be useful for identifying individuals at risk for PD and for identifying signaling pathways that are disrupted in PD. We are testing the expression of the biomarkers in RNA prepared from whole blood of hyposmic participants in the Parkinson's Associated Risk Study (PARS) (Technical Objective 1.0). In order to establish a model for testing the function of the biomarkers, we are determining whether their expression is altered in human olfactory neurosphere-derived (hONS) cells derived from idiopathic PD patients and healthy controls (Technical Objective 2.0). To determine the signaling pathways affected in PD and identify additional biomarkers, we are using network analysis (Technical Objective 3.0). During year 1, RNA and cDNA was prepared from PARS samples from Year 0 (baseline) and Year 2. Quantitative polymerase chain reactions were initiated for two of the biomarkers (APP, HNF4α). Expression of the biomarkers was tested in hONS. We also developed network approaches to reveal the common molecular pathways involved with PD and type 2 diabetes (T2DM). Using these networks, we identified APP, HNF4A and SOD2 mRNAs as blood biomarkers predictive of early stage PD. In addition, we determined that HNF4A mRNA may be a progression marker in blood for PD. SUBJECT TERMSParkinson's disease, biomarkers, neurodegeneration, network and pathway analysis 12-15Santiago 16-23Sei...

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Rosiglitazone acts as a neuroprotectant in retinal cells via up‐regulation of sestrin‐1 and SOD‐2

Cited by 36 publications

References 39 publications

DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

Anti-apoptotic Actions of PPAR-γ Against Ischemic Stroke

Splice Variant Biomarkers for Parkinson's Disease

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