Zsofia Digby

Anti-Inflammatory Effects of Oral NLRP3 Inhibition With Ruvonoflast Among Individuals at Elevated Cardiovascular Risk

Kausik K. Ray, Nicholas P. Clarke, Peter Thornton, Amy E. Miles et autres

BACKGROUND: The nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a key sensor of diverse exogenous stimuli linked to noncommunicable diseases including atherosclerotic cardiovascular disease. Early clinical data with the oral NLRP3 inhibitor ruvonoflast suggested lowering of …

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Ester Prodrug NLRP3 Inflammasome Inhibitor NT-0796 is Brain Active due to Activation by Local Expression of Carboxylesterase-1

Zsofia Digby, Christine Diamond, Heather Wescott, Pam Smolak et autres

High Resolution Image Download MS PowerPoint Slide NLRP3 inflammasome activation has been implicated in the pathogenesis of human disorders, including a number of neurodegenerative diseases of the central nervous system. Pharmacological inhibition of NLRP3-mediated neuroinflammation via a brain-penetrant therapeutic agent, therefore, is …

Anti‐Neuroinflammatory and Anti‐Inflammatory Effects of the NLRP3 Inhibitor NT ‐0796 in Subjects with Parkinson's Disease

Nicholas P. Clarke, Peter Thornton, Valérie Reader, Nicola A. Lindsay et autres

BACKGROUND: Inhibition of Nod-like receptor protein 3 (NLRP3) inflammasome within the central nervous system (CNS) is a promising therapeutic target for the treatment of Parkinson's disease (PD). OBJECTIVES: This phase 1b open-label study was conducted in elderly healthy volunteers (HV) and PD …

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The NLRP3 inhibitor NT ‐0796 enhances and sustains GLP ‐ 1R agonist‐mediated weight loss in a murine diet‐induced obesity model

Peter Thornton, Valérie Reader, Zsofia Digby, John R. Doedens et autres

OBJECTIVE: In order to investigate whether a central nervous system penetrant anti-inflammatory could augment or sustain obesity treatment with semaglutide (Wegovy), a glucagon-like peptide-1 receptor (GLP-1R) agonist, we tested two hypotheses in models of diet-induced obesity (DIO): 1) a centrally penetrant NLPR3 …

Profile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as an in vivo tool compound for neuroinflammatory disorders

David Harrison, Andy Billinton, Mark G. Bock, Nicholas P. Clarke et autres

model of inflammation, and with good developability characteristics. However, NT-0527 exhibited CYP 2C19 time-dependent inhibition, which halted development, but this molecule could be employed as a valuable tool compound for the investigation of neuroinflammatory conditions where NLRP3 inflammasome activation is implicated.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796

Peter Thornton, Valérie Reader, Zsofia Digby, Pamela J. Smolak et autres

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of …

Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections

Zsofia Digby, Panagiotis Tourlomousis, James Rooney, Joseph P. Boyle et autres

Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive …

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Zebrafish Developmental Stage 3' end data (GRCz11/e92)

Richard Joseph White, John E Collins, Ian M. Sealy, Neha Wali et autres

This contains the DeTCT data presented in White et al. 2017 (https://doi.org/10.7554/eLife.30860) mapped to the GRCz11 assembly and counted against the Ensembl version 92 annotation. Descriptions of each file are in the README.md file

Caspase isoforms in inflammasome activation

Zsofia Digby

Inflammasomes are macromolecular signalling platforms composed of a receptor (for example NLRP3 or NLRC4), an adaptor (ASC) and effectors (caspases) that are thought to play critical roles in the host defence against microbial infections. Activation of inflammasomes leads to the processing of …

Zebrafish Developmental Stages RNA-seq count data (GRCZ11)

Richard Joseph White, John E Collins, Ian M. Sealy, Neha Wali et autres

Count data generated from RNA-seq from zebrafish embryos from 18 developmental stages from 1-cell to 5 dpf (White et al. 2017, http://dx.doi.org/10.7554/eLife.30860) mapped to the GRCz11 assembly.

The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish

Catherine M. Scahill, Zsofia Digby, Ian M. Sealy, Richard Joseph White et autres

Background: Mutations in proteins involved in telomere maintenance lead to a range of human diseases, including dyskeratosis congenita, idiopathic pulmonary fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the ends of chromosomes, however non-canonical roles of components of telomerase …

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Raw data of Fertilisation Rates

Catherine M. Scahill, Zsofia Digby, Ian M. Sealy, Richard Joseph White et autres

Data on fertilisation and phenotype rates of clutches laid by wild-type and heterozygous tertsa6541 intercrosses.