A5071643580- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Quinazolinone synthesis and applications
- Spectroscopy and Chemometric Analyses
- Phenothiazines and Benzothiazines Synthesis and Activities
- Melanoma and MAPK Pathways
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Plant Virus Research Studies
- Optical Coherence Tomography Applications
- Memory and Neural Mechanisms
- GABA and Rice Research
- Synthesis and Biological Evaluation
- Epilepsy research and treatment
- Immune Cell Function and Interaction
- Spectroscopy Techniques in Biomedical and Chemical Research
- Signaling Pathways in Disease
MRC Laboratory of Molecular Biology
2022-2024
University of Southampton
2018-2023
Abstract Phosphorylation of the translation initiation factor eIF2α to initiate integrated stress response (ISR) is a vital signalling event. Protein kinases activating ISR, including PERK and GCN2, have attracted considerable attention for drug development. Here we find that widely used ATP-competitive inhibitors PERK, GSK2656157, GSK2606414 AMG44, inhibit in nanomolar range, but surprisingly activate ISR via GCN2 at micromolar concentrations. Similarly, PKR inhibitor, C16, also activates...
Abstract We report a technologically novel microscopy system for bioimaging based on 100 fs titanium:sapphire (Ti:Sa) laser pumped coherent continuum from tailored, 9-cm long, all normal dispersion (ANDi) fiber, enabling concurrent image contrast with (a) spectral focusing anti-Stokes Raman scattering (SF-CARS) (spanning 900–3200 cm −1 ) and (b) sum frequency generation (SFG). Both modalities were efficiently excited power levels at the microscope focus compatible biological samples....
The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience protect cells from challenges. Here, we investigated whether increasing ISR could rescue diabetes-like phenotypes in mouse model of diet-induced obesity (DIO). We show the orally available clinically approved GCN2 activator halofuginone (HF) can activate tissues. found daily oral administration HF increases glucose tolerance whilst reducing...
Article25 April 2022Open Access Transparent process Cellular responses to halofuginone reveal a vulnerability of the GCN2 branch integrated stress response Aleksandra P Pitera orcid.org/0000-0001-7004-1615 MRC Laboratory Molecular Biology, Cambridge, UK Contribution: Conceptualization, Formal analysis, Validation, Investigation, Visualization, Writing - review & editing Search for more papers by this author Maria Szaruga orcid.org/0000-0003-1673-1855 Sew-Yeu Peak-Chew...
Glutamate receptors of the N-methyl-D-aspartate (NMDA) family are coincident detectors pre- and postsynaptic activity, allowing Ca2+ influx into neurons. These properties central to neurological disease mechanisms proposed be basis associative learning memory. In addition well-characterised canonical GluN2A NMDAR isoform, large-scale open reading frames in human tissues had suggested expression a primate-specific short isoform referred as GluN2A-S. Here, we confirm both transcripts primate...
Tauopathies are a group of neurodegenerative diseases associated with the accumulation misfolded tau protein. The mechanisms underpinning tau-dependent proteinopathy remain to be elucidated. A protein quality control pathway within endoplasmic reticulum, unfolded response (UPR), has been suggested as possible modulating cellular responses in range diseases, including those cytosolic tau. In this study we investigated three different clinically defined tauopathies establish whether these...
Abstract Background The Gadd45 family are a set of 3 genes classically induced by DNA damage. They also wider stresses such as axonal injury, ischemia and degenerative diseases like ALS. Increased protein staining is observed in AD brains, however their association with pathogenic tau unknown. undergo alternative splicing to generate 8 functionally distinct proteins, whose significance neuronal systems poorly understood. We aim investigate if the upregulated tauopathies whether this...
Abstract Tauopathies are the neurodegenerative diseases associated with accumulation of misfolded tau protein. Despite many years investigation, mechanisms underpinning dependent proteinopathy remains to be elucidated. A protein quality control pathway within endoplasmic reticulum (ER), called unfolded response (UPR), has been suggested as a possible implicated in tau-mediated neurodegeneration. However, question arose: how does cytosolic that not enter ER induce stemming from this...