A5028967759- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Olfactory and Sensory Function Studies
- Neuroscience and Neural Engineering
- EEG and Brain-Computer Interfaces
- Coenzyme Q10 studies and effects
- Neurogenetic and Muscular Disorders Research
- Wnt/β-catenin signaling in development and cancer
- Prion Diseases and Protein Misfolding
King's College London
2013-2022
Alzheimer’s Research UK
2022
University College London
2022
Neuroscience Institute
2019
Propagation of tau pathology is linked with progressive neurodegeneration, but the mechanism underlying trans‐synaptic spread unknown. We show that stimulation neuronal activity, or AMPA receptor activation, induces release from healthy, mature cortical neurons. Notably, phosphorylation extracellular appears reduced in comparison intracellular tau. also find AMPA‐induced calcium‐dependent. Blocking pre‐synaptic vesicle by tetanus toxin and inhibiting activity tetrodotoxin both significantly...
Article14 July 2016Open Access Transparent process ALS/FTD-associated FUS activates GSK-3β to disrupt the VAPB–PTPIP51 interaction and ER–mitochondria associations Radu Stoica Department of Basic Clinical Neuroscience, Institute Psychiatry, Psychology Kings College London, UK Search for more papers by this author Sébastien Paillusson Patricia Gomez-Suaga Jacqueline C Mitchell Dawn HW Lau Emma H Gray Rosa M Sancho Gema Vizcay-Barrena Centre Ultrastructural Imaging, King's Kurt J De Vos...
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...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuropathological deposits of amyloid plaques and neurofibrillary tangles comprised β-amyloid tau protein, respectively. In AD, becomes abnormally phosphorylated aggregates to form intracellular deposits. However, the mechanisms which exerts neurotoxicity in remain unclear. Recent studies have suggested that presence at synapses may indicate role neuronal signalling, could be disrupted pathological...
Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of key neuronal functions, many which are perturbed in Alzheimer's disease. Moreover, damage to ER-mitochondria signaling is seen cell transgenic models However, as yet there little evidence that altered human disease brains. mediated by interactions integral ER protein VAPB outer mitochondrial membrane PTPIP51 act recruit "tether" regions surface. The VAPB-PTPIP51 tethers now known regulate functions...
Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results overt hypophosphorylation and age-dependent alterations axonal mitochondrial transport peripheral nerves. To determine effects P301L expression central nervous system, we examined kinetics phosphorylation primary cortical neurons from knock-in (KI-P301L) mice. We observed a significant 50% reduction number mitochondria axons cultured KI-P301L mice...
Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many neuronal functions that are perturbed in amyotrophic lateral sclerosis (ALS) perturbation to ER-mitochondria signaling is seen cell transgenic models of ALS. However, there currently little evidence altered human mediated by interactions integral ER protein VAPB outer mitochondrial membrane PTPIP51 which act recruit “tether” regions surface. The VAPB-PTPI51 tethers now known regulate a number functions. These...
Abstract Damage to axonal transport is an early pathogenic event in Alzheimer’s disease. The amyloid precursor protein (APP) a key cargo since disruption APP promotes amyloidogenic processing of APP. Moreover, altered itself disrupts transport. mechanisms that regulate are therefore directly relevant disease pathogenesis. transported anterogradely through axons on kinesin-1 motors and one route for this involves calsyntenin-1, type-1 membrane spanning acts as direct ligand light chains...
Abstract Polymorphisms associated with BIN1 (bridging integrator 1) confer the second greatest risk for developing late-onset Alzheimer’s disease. The biological consequences of this genetic variation are not fully understood; however, is a binding partner tau. Tau normally highly soluble cytoplasmic protein, but in disease, tau abnormally phosphorylated and accumulates at synapses to exert synaptotoxicity. purpose study was determine whether alterations disease promote damaging...
Cyclin dependent kinase-5 (cdk5)/p35 is a neuronal kinase that regulates key axonal and synaptic functions but the mechanisms by which it transported to these locations are unknown. Lemur tyrosine kinase-2 (LMTK2) binding partner for p35 here we show LMTK2 also interacts with kinesin-1 light chains (KLC1/2). Binding KLC1/2 involves C-terminal tryptophan/aspartate (WD) motif in tetratricopeptide repeat (TPR) domains KLC1/2, this interaction facilitates transport of LMTK2. Thus, siRNA loss...
Neuroinflammation and hyperexcitability have been implicated in the pathogenesis of neurodegenerative disease, new models are required to investigate cellular crosstalk involved these processes. We developed an approach generate a quantitative reproducible triculture system that is suitable for pharmacological studies. While primary rat cells were previously grown coculture medium formulated support only neurons astrocytes, we now optimised protocol tricultures containing neurons, astrocytes...
Abstract Background Post-translational modifications of tau modify its interaction with binding partners and cause mislocalisation altered function in Alzheimer’s disease (AD). The AD risk gene BIN1, is a partner for tau, however the mechanism by which BIN1 influences not fully understood. We hypothesised that modulates causing damaging mis-sorting to synapse. Methods Tau levels, distribution interactions were assessed post-mortem control brain primary neurons. In neurons, was further...
Under pathological conditions, tau is abnormally phosphorylated and sequestered into intracellular aggregates in Alzheimer's disease (AD). Tau-containing neurofibrillary tangles, together with plaques containing β-amyloid, form the neuropathological hallmarks of AD. Fyn a member Src family non-receptor-associated tyrosine kinases, which upregulated subset neurons from AD brain also contain aggregated tau. normally found dendrites, where it localises mediates synaptic stability. We have...
In Alzheimer's disease, the cytoskeletal protein tau becomes hyperphosphorylated, and forms into aggregates intracellular tangles. These neuropathological deposits of spread progressively from entorhinal cortex to anatomically connected regions brain. Propagation pathology is associated with progressive neurodegeneration, but mechanism underlying trans-synaptic has yet be elucidated. Objective: To determine whether neurons release endogenous tau, by which this may occur. We analyzed released...
The pathological progression of tau through the brain in Alzheimer's disease and related tauopathies appears to involve cell-to-cell transmission aggregated tau. spread may be initiated by a potential seeding mechanism which uptake pathogenic species results neurodegeneration affected regions. Tau between neurons also occurs trans-synaptically, suggesting that propagation is an active process associated with synapses. release from cultured cortical organotypic slice cultures under basal...
Abstract Neuroinflammation and hyperexcitability have been implicated in the pathogenesis of neurodegenerative disease, new models are required to investigate cellular crosstalk involved these processes. We developed an approach generate a quantitative reproducible triculture system that is suitable for pharmacological studies. While primary rodent cells were previously grown coculture medium formulated support only neurons astrocytes, we now optimised protocol tricultures containing...