A5032753911- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Adenosine and Purinergic Signaling
- Stress Responses and Cortisol
- Neurogenesis and neuroplasticity mechanisms
- Cannabis and Cannabinoid Research
- Peroxisome Proliferator-Activated Receptors
- Cholinesterase and Neurodegenerative Diseases
- S100 Proteins and Annexins
- Mitochondrial Function and Pathology
- Anesthesia and Neurotoxicity Research
- Inflammatory mediators and NSAID effects
- Cholesterol and Lipid Metabolism
- Genetics and Neurodevelopmental Disorders
- Neuroendocrine regulation and behavior
- Endoplasmic Reticulum Stress and Disease
- Neuroscience of respiration and sleep
- Eicosanoids and Hypertension Pharmacology
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Retinal Diseases and Treatments
- Inflammation biomarkers and pathways
- Neurological Complications and Syndromes
King's College London
2016-2024
Massachusetts General Hospital
2013-2021
Neuroscience Institute
2019
Harvard University
2011-2018
AstraZeneca (United Kingdom)
2017
Universidad Complutense de Madrid
2006-2015
Centro de Investigación Biomédica en Red de Salud Mental
2010-2015
Instituto de Salud Carlos III
2015
Research Institute Hospital 12 de Octubre
2011-2015
University of Bonn
2010
Clinico-pathological correlation studies and positron emission tomography amyloid imaging have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype these unique cases might prove relevant to understanding human resilience pathology. We conducted detailed quantitative histopathological biochemical assessments on from non-demented before death whose were...
Research Article30 August 2017Open Access Source DataTransparent process TREM2 shedding by cleavage at the H157-S158 bond is accelerated for Alzheimer's disease-associated H157Y variant Peter Thornton Neuroscience, Innovative Medicines and Early Development, AstraZeneca, Granta Park, Cambridge, UK Search more papers this author Jean Sevalle Tanz Centre in Neurodegenerative Diseases, University of Toronto, ON, Canada Michael J Deery Cambridge Proteomics, UKCorrection added on 2 October 2017...
Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of key neuronal functions. This signaling involves close physical contacts two organelles that are mediated by "tethering proteins" function to recruit regions ER mitochondrial surface. The protein, vesicle-associated membrane protein-associated protein B (VAPB) tyrosine phosphatase interacting protein-51 (PTPIP51), interact form one such tether. Recently, damage ER-mitochondria involving disruption...
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding mechanisms mediating inhibition in conditions therefore direct design drugs targeted these diseases with minimal side-effects. Our study provides first vivo evidence that specific Keap1,...
Alterations in calcium homeostasis are widely reported to contribute synaptic degeneration and neuronal loss Alzheimer's disease. Elevated cytosolic concentrations lead activation of the calcium-sensitive cysteine protease, calpain, which has a number substrates known be abnormally regulated Analysis human brain shown that calpain activity is elevated AD compared controls, calpain-mediated proteolysis regulates important disease-associated proteins including tau kinases cyclin-dependent...
Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques intracellular tau neurofibrillary tangles Alzheimer's disease (AD). In addition, AD is characterized an increase astrocyte reactivity. The chaperone HSPB1 has been proposed a marker for reactive astrocytes; however, its astrocytic functions neurodegeneration remain to be elucidated. Here, we identify that secreted from astrocytes exert...
Background Chronic pain and depression are two complex states with sensory/somatic emotional components, they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis. Methods The authors have evaluated the sensory components rat model combining chronic constriction injury (CCI, neuropathic pain) unpredictable mild stress (CMS, an experimental depression). In addition, phosphorylation/activation extracellular signal-regulated kinases 1 2 neuronal...
Abstract Alzheimer’s disease (AD) is characterised by Aβ and tau pathology as well synaptic degeneration, which correlates best with cognitive impairment. Previous work suggested that this pathological complexity may result from changes in mRNA translation. Here, we studied whether translation its underlying signalling are altered an early model of AD, modelling deficiency mice causes features ageing. Using unbiased screen, show exposure primary neurons to nanomolar amounts increases...
Stress exposure leads to oxidative/nitrosative and neuroinflammatory changes that have been shown be regulated by antiinflammatory pathways in the brain. In particular, acute restraint stress is followed cyclooxygenase (COX)-2 up-regulation subsequent proinflammatory prostaglandin (PG) E2 release rat brain cortex. Concomitantly, synthesis of 15d-PGJ2 activation its nuclear target peroxisome proliferator-activated receptor (PPAR)-γ are also produced. This study aimed determine possible role...
Among Alzheimer's disease (AD) brain hallmarks, the presence of reactive astrocytes was demonstrated to correlate with neuronal loss and cognitive deficits. Evidence indeed supports role as mediators changes in neurons, including synapses. However, complexity outcomes astrocyte reactivity are far from being completely elucidated. Another key AD pathogenesis is played by alterations cholesterol metabolism. Oxysterols (cholesterol oxidation products) crucial for homeostasis, we previously that...
purpose. To evaluate the possible correlation between visual field defects in patients with primary open-angle glaucoma (POAG) and expression enzymatic activity of nitric oxide synthase (NOS) isoenzymes nitrotyrosine trabecular meshwork (TM) samples. methods. TM specimens were collected from 146 POAG by using standard filtration surgery. Visual evaluated perimetry. Expression endothelial (e)NOS inducible (i)NOS quantitative RT-PCR. Constitutive (Ca2+-dependent) iNOS (Ca2+-independent)...
The deleterious effects of stress on the gastrointestinal tract seem to be mainly mediated by induction intestinal barrier dysfunction and subsequent subtle mucosal inflammation. Cannabinoid 1 receptor (CB1R) is expressed in mammalian gut under physiological circumstances. aim this investigation study possible role CB1R maintenance homeostasis after exposure. knockout mice (CB1R(-/-)) their wild-type (WT) counterparts were exposed immobilization acoustic (IA) for 2 h per day during 4...
Diabetes increases cardiac damage after myocardial ischaemia. Cannabinoids can protect against ischaemia/reperfusion injury. The aim of this study was to examine the cardioprotective effect cannabinoid agonist WIN 55,212-2 (WIN) injury in an experimental model type 2 diabetes. We performed these experiments Zucker diabetic fatty rat, and focused on role receptors modulation inducible nitric oxide synthase (iNOS)/endothelial-type (eNOS) expression.Male 20-week-old rats were treated with...
Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many these patients also experience stress unrelated to illness, can aggravate symptoms. These nociceptive inputs are received by the hippocampus, in maladaptive neuroplastic changes may occur conditions pain. The hippocampus is a structure involved emotionality, learning, memory, proliferating cells granular layer hippocampal dentate gyrus...
It has been suggested that aberrant activation of glycogen synthase kinase-3-beta (GSK-3β) can trigger abnormal tau hyperphosphorylation and aggregation, which ultimately leads to neuronal/synaptic damage impaired cognition in Alzheimer disease (AD). We examined if isoform-selective partial reduction GSK-3β decrease pathological changes, including hyperphosphorylation, spreading, mice with localized human wild-type (hTau) expression the brain. used adeno-associated viruses (AAVs) express...