A5035986686- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Microtubule and mitosis dynamics
- Autophagy in Disease and Therapy
- Cholinesterase and Neurodegenerative Diseases
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Machine Learning in Bioinformatics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Estrogen and related hormone effects
- Neurogenetic and Muscular Disorders Research
- Medicinal Plants and Neuroprotection
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Aluminum toxicity and tolerance in plants and animals
- S100 Proteins and Annexins
- Chemical Synthesis and Analysis
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- RNA regulation and disease
King's College London
2013-2025
Semmelweis University
2024
Montavid Thermodynamic Research Group
2024
Eötvös Loránd University
2010
A proline to serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB) causes some dominantly inherited familial forms of motor neuron disease including amyotrophic lateral sclerosis (ALS) type-8. VAPB is an integral endoplasmic reticulum (ER) whose amino-terminus projects into cytosol. Overexpression ALS mutant VAPBP56S disrupts ER structure but mechanisms by which it induces are not properly understood. Here we show that...
A proline-to-serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; VAPBP56S) causes some dominantly inherited familial forms of motor neuron disease, including amyotrophic lateral sclerosis (ALS) type-8. Here, we show that expression ALS mutant VAPBP56S but not wild-type VAPB neurons selectively disrupts anterograde axonal transport mitochondria. VAPBP56S-induced disruption mitochondrial involved reductions frequency, velocity...
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...
Abstract Hexanucleotide repeat expansions in C9orf72 are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mechanisms by which disease not properly understood but a favoured route involves its translation into dipeptide (DPR) polypeptides, some neurotoxic. However, precise targets for mutant DPR toxicity fully clear, damage to several neuronal functions has been described. Many these regulated signalling between endoplasmic reticulum...
Abstract Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are clinically linked major neurodegenerative diseases. Notably, TAR DNA-binding protein-43 (TDP43) accumulations hallmark pathologies of FTD/ALS mutations in the gene encoding TDP43 cause familial FTD/ALS. There no cures for display damage to a broad range physiological functions, many which regulated by signaling between endoplasmic reticulum (ER) mitochondria. This is mediated VAPB-PTPIP51 tethering proteins...
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...
Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of fundamental physiological processes. This signaling involves close physical contacts two organelles that are mediated by VAPB-PTPIP51 ″tethering” proteins. The tethers facilitate inositol 1,4,5-trisphosphate (IP3) receptor delivery Ca 2+ from ER to mitochondria. Damage is seen in Alzheimer’s disease, Parkinson’s disease frontotemporal dementia with related amyotrophic lateral sclerosis (FTD/ALS)....
FE65 is an adaptor protein that binds to the amyloid precursor (APP). As such, has been implicated in pathogenesis of Alzheimer's disease. In addition, evidence suggests involved brain development. It generally believed participates these processes by recruiting various interacting partners form functional complexes. Here, we show via its first phosphotyrosine binding (PTB) domain, small GTPase ADP-ribosylation factor 6 (ARF6). preferentially ARF6-GDP, and they colocalize neuronal growth...
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...
Alzheimer disease is characterized by accumulation of β-amyloid (Aβ) and cognitive dysfunctions linked to early loss cholinergic neurons. As estrogen-based hormone replacement therapy has beneficial effects on cognition demented patients, it may prevent memory impairments, we investigated the effect estrogen-pretreatment Aβ-induced neurodegeneration in nucleus basalis magnocellularis (NBM). We tested which Aβ species induces more pronounced cholinotoxic vivo. injected different assemblies...
Abstract Background Cardiac remodelling, a crucial aspect of heart failure, is commonly investigated in preclinical models by quantifying cardiomyocyte cross‐sectional area (CSA) and microvascular density (MVD) via histological methods, such as immunohistochemistry. To achieve this, optimized protocols are needed, the species specificity dependent on antibody used. Lectin histochemistry offers several advantages compared to antibody‐based immunohistochemistry, including cost‐effectiveness...