Explanipedia

Azathioprine for the treatment of early Parkinson's disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial Open

Julia C. Greenland, Kerry Dresser, Emma Cutting, Rachel Donegan, Simon Bond , et al. · 2025

Constipation Is Linked to Neuroinflammation in Early Parkinson's Disease Open

Alexander R. D. Peattie, Jonathan Holbrook, Lakmini Kahanawita, Young T. Hong, Caroline H. Williams‐Gray · 2025

Background Constipation is a risk factor for the onset and accelerated progression of Parkinson's disease (PD), but the mechanisms underlying this association are unknown. Neuroinflammation in PD has been demonstrated in postmortem and neu…

Efficacy and potential human and economic impact of a broadly protective betacoronavirus vaccine Open

George Carnell, Robert Vendramelli, Charles Whittaker, Jonathan Holbrook, Srivatsan Parthasarathy , et al. · 2025

Within two decades, three different betacoronaviruses (β-CoV) have spilled over from animals to humans causing high consequence diseases, the most recent causing the COVID-19 pandemic. Using computational antigen design technology, we deve…

Peripheral-central immune crosstalk in Parkinson’s disease and its association with clinical severity Open

Julia C. Greenland, Jonathan Holbrook, Lakmini Kahanawita, Marta Camacho, Tim D. Fryer , et al. · 2025

This exploratory study suggests that peripheral and central immune changes are closely linked in PD, and relevant to clinical disease severity. These findings warrant further validation and exploration to identify immune biomarkers linked …

A 14‐Year Study of Serum Glial Fibrillary Acidic Protein and Total Tau in Premanifest Huntington's Open

Natalia E. Owen, Zanna J. Voysey, Jonathan Holbrook, Maura Malpetti, Clara Le Draoulec , et al. · 2025

There is a pressing need for blood biomarkers that can identify Huntington's disease (HD) gene carriers' proximity to manifest disease. We previously examined serial serum neurofilament light (NfL) concentrations in 21 premanifest HD gene …

Covering All Bases: A Computational Method to Design Broad-spectrum T-cell-inducing Vaccines Applied to <i>Betacoronaviruses</i> Open

Phil Palmer, Sofiya Fedosyuk, Srivatsan Parthasarathy, Jonathan Holbrook, Charlotte George , et al. · 2025

Antigenically diverse pathogens, such as coronaviruses, pose substantial threats to global health. This highlights the need for effective broad-spectrum vaccines that elicit robust immune responses in a large proportion of the human popula…

Natural killer cells have an activated profile in early Parkinson's disease Open

Jonathan Holbrook, Bhavana Patel, Marta Camacho, L. Kahanawita, Julia C. Greenland , et al. · 2023

Immune dysregulation is heavily implicated in Parkinson's disease (PD) but the role of Natural Killer (NK) cells has not been well characterised. Accumulating evidence indicates the immune response peaks early in the disease, hence this st…

Neurodegenerative Disease and the NLRP3 Inflammasome Open

Jonathan Holbrook, Heledd Jarosz-Griffiths, Emily A. Caseley, Samuel Lara‐Reyna, James A. Poulter , et al. · 2021

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the…

Relation of Magnetic Resonance Imaging Based Arterial Signal Enhancement to Markers of Peripheral Artery Disease Open

Olga A. Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M. Short, Addison A. Taylor , et al. · 2020

WS12.6 Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis Open

Heledd Jarosz-Griffiths, Thomas Scambler, Cindy Wong, Samuel Lara‐Reyna, Jonathan Holbrook , et al. · 2020

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations Open

Samuel Lara‐Reyna, Jonathan Holbrook, Heledd Jarosz-Griffiths, D. Peckham, Michael McDermott · 2020

Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis Open

Heledd Jarosz-Griffiths, Thomas Scambler, Chi Huey Wong, Samuel Lara‐Reyna, Jonathan Holbrook , et al. · 2020

Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature with increased IL-18, IL-1β, caspase-1 activity and ASC speck release (Scambler et al. eLife 2019). Here we show that CFT…

Author response: Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis Open

Heledd Jarosz-Griffiths, Thomas Scambler, Chi Huey Wong, Samuel Lara‐Reyna, Jonathan Holbrook , et al. · 2020

ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis Open

Thomas Scambler, Heledd Jarosz-Griffiths, Samuel Lara‐Reyna, Shelly Pathak, Chi Huey Wong , et al. · 2019

Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR-mediated chloride and bicarbonate transport, with dysregulation of epitheli…

Author response: ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis Open

Thomas Scambler, Heledd Jarosz-Griffiths, Samuel Lara‐Reyna, Shelly Pathak, Chi Huey Wong , et al. · 2019

Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Cystic Fibrosis (CF) is a monogenic diseas…

Metabolic Reprograming of Cystic Fibrosis Macrophages via the IRE1α Arm of the Unfolded Protein Response Results in Exacerbated Inflammation Open

Samuel Lara‐Reyna, Thomas Scambler, Jonathan Holbrook, Chi Huey Wong, Heledd Jarosz-Griffiths , et al. · 2019

Cystic Fibrosis (CF) is a recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR mutations cause dysregulation of channel function with intracellular accumulation of misfolded…

Tumour necrosis factor signalling in health and disease Open

Jonathan Holbrook, Samuel Lara‐Reyna, Heledd Jarosz-Griffiths, Michael McDermott · 2019

The master pro-inflammatory cytokine, tumour necrosis factor (TNF), has been shown to modulate multiple signalling pathways, with wide-ranging downstream effects. TNF plays a vital role in the typical immune response through the regulation…

Excessive ENaC-mediated sodium influx drives NLRP3 inflammasome-dependent autoinflammation in cystic fibrosis Open

Thomas Scambler, Heledd Jarosz-Griffiths, Samuel Lara‐Reyna, Shelly Pathak, Chi Huey Wong , et al. · 2018

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and results in defective CFTR-mediated chloride transport, dysregulation of epithelial sodium channels (ENaC) and exaggerate…

The effect of cysteamine and epigallocatechin gallate on the inflammatory phenotype in cystic fibrosis Open

Jonathan Holbrook, Thomas Scambler, S Lara Reyna, Cindy Wong, Heledd Jarosz-Griffiths , et al. · 2018

EPS1.06 Overproduction of IL-6 and TNF through IRE1α is CFTR genotype dependent Open

S Lara Reyna, Thomas Scambler, Jonathan Holbrook, Chi Huey Wong, Heledd Jarosz-Griffiths , et al. · 2018

WS04.3 Sodium influx modulates innate immune inflammation and metabolism in cystic fibrosis Open

Thomas Scambler, Chi Huey Wong, Shelly Pathak, S Lara Reyna, Jonathan Holbrook , et al. · 2018

WS04.5 The effect of cysteamine and epigallocatechin gallate on hyperresponsive inflammation in cystic fibrosis Open

Jonathan Holbrook, Thomas Scambler, Samuel Lara‐Reyna, Chi Huey Wong, Heledd Jarosz-Griffiths , et al. · 2018

Autoinflammatory disease in the lung Open

Thomas Scambler, Jonathan Holbrook, Sinisa Savic, Michael McDermott, D. Peckham · 2018

Summary Ascertaining the dominant cell type driving an immunological disease is essential to understanding the causal pathology and, therefore, selecting or developing an effective treatment. Classifying immunological diseases in this way …

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