A5047432836- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Dementia and Cognitive Impairment Research
- Nerve injury and regeneration
- Medicinal Plants and Neuroprotection
- Neurological Disorders and Treatments
- Phosphodiesterase function and regulation
- 14-3-3 protein interactions
- Tryptophan and brain disorders
- S100 Proteins and Annexins
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Molecular spectroscopy and chirality
- Glaucoma and retinal disorders
- Biochemical Acid Research Studies
- Treatment of Major Depression
- Neuroscience and Neural Engineering
- Protein Structure and Dynamics
- ATP Synthase and ATPases Research
- Receptor Mechanisms and Signaling
Karolinska Institutet
2016-2025
University of Iceland
2020
National University Hospital of Iceland
2020
deCODE Genetics (Iceland)
2020
Reykjavík University
2020
Alzheimer’s Disease Neuroimaging Initiative
2016
Karolinska University Hospital
2006-2015
Novartis (United States)
2013
Hebrew University of Jerusalem
2002
Wenner-Gren Foundations
2001
The accumulation of β-amyloid in the brain is an early event Alzheimer's disease. This study presents first patient with disease who underwent positron emission tomography imaging amyloid tracer, Pittsburgh Compound B to visualize fibrillar brain. Here we relate clinical progression, and functional molecular neuropathological alterations at autopsy gain new insight into relationship between accumulation, inflammatory processes cholinergic neurotransmitter system studies...
Abstract Background Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer’s disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis been tested in patients with AD using encapsulated cell biodelivery NGF (NGF-ECB) first-in-human study. We report our results from third-dose cohort receiving second-generation NGF-ECB implants improved secretion. Methods Four mild moderate were recruited participate an...
The native function of amyloid-β (Aβ) peptides is still unexplored. However, several recent reports suggest a prominent role Aβ in acetylcholine homeostasis. To clarify this Aβ, we have reported that at physiological concentrations can directly enhance the catalytic efficiency key cholinergic enzyme, choline acetyltransferase (ChAT), via an allosteric interaction. In current study, further aimed to elucidate underlying ChAT-Aβ interaction mechanism using silico molecular docking and dynamics...
<b><i><i>Objective:</i></i></b> To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with AD. <b><i>Methods:</i></b> Eleven mild AD received for 12 months. Cholinesterase (ChE) activities CSF plasma were assessed colorimetrically. Immunoblot analysis was used to evaluate AChE isoforms. Neuropsychiatric tests performed throughout study. <b><i>Results:</i></b> At months, mean dose 8.6 mg/d specific ChE lower...
Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both nervous system secondary lymphoid organs. Most these cells are very distant from cholinergic synapses. The action ACh on is unlikely to occur through diffusion, given that short-lived presence acetylcholinesterase (AChE) butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present extracellular...
New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective on basal forebrain cholinergic neurons in animal studi
Abstract Introduction Several pharmacoepidemiological studies indicate that proton pump inhibitors (PPIs) significantly increase the risk of dementia. Yet, underlying mechanism is not known. Here, we report discovery an unprecedented mode action PPIs explains how may Methods Advanced in silico docking analyses and detailed enzymological assessments were performed on against core‐cholinergic enzyme, choline‐acetyltransferase (ChAT), responsible for biosynthesis acetylcholine (ACh). Results...
Various pharmacoepidemiological investigational studies have indicated that Proton Pump Inhibitors (PPIs) may increase the likelihood of developing Alzheimer's disease (AD) and non-AD related dementias. Previously, we reported inhibition acetylcholine biosynthesizing enzyme choline acetyltransferase (ChAT) by PPIs, for which omeprazole, lansoprazole, pantoprazole exhibited IC50 values 0.1, 1.5, 5.3 μM, respectively. In this study utilize a battery computational tools to perceive mechanistic...
Abstract Protein levels of different acetylcholinesterase (AChE) splice variants were explored by a combination immunoblot techniques, using two antibodies, directed against the C‐terminus AChE‐R variant or core domain common to all variants. Both and AChE‐S as well several heavier AChE complexes detected in brain homogenates from parietal cortex patients with without Alzheimer's disease (AD) cerebrospinal fluid (CSF) AD patients, compatible assumption that CSF AChEs might originate CNS...
The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities protein levels, in cerebrospinal fluid (CSF) Alzheimer disease (AD) patients.AD patients aged 50-85 years were randomized open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE BuChE assayed by Ellman's colorimetric method. Protein levels assessed enzyme-linked immunosorbent assay (ELISA). Primary...
Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating activation remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation C3 immediately downstream butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), classical neurotransmitter with immunoregulatory effects. We here determined levels neurofilament-light (NFL), marker for ongoing nerve injury, activity two main ACh...
Dimethyl sulfoxide (DMSO) is the most common organic solvent used in biochemical and cellular assays during drug discovery programs. Despite its wide use, effect of DMSO on several enzyme classes, which are crucial targets new therapeutic agents, still unexplored. Here, we report detailed analysis effects human acetylcholine-degrading enzyme, acetylcholinesterase (AChE), primary target current Alzheimer's therapeutics. Our showed that a considerably potent highly selective irreversible...
Abstract Introduction The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. cardinal biomarker the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found cerebrospinal fluid (CSF). purpose this study was see if EC‐NGF therapy will alter CSF levels biomarkers, ChAT, and acetylcholinesterase. Method Encapsulated cell implants releasing NGF (EC‐NGF) were...
Changes in cerebrospinal fluid (CSF) biomarkers are representative of biochemical changes the brain. Collection CSF by lumbar puncture (LP) is essential for biomarker analysis, which important research neurodegenerative disorders. However, LP purposes has been controversial due to a reported high incidence severe headache when using standard 18g or 20g Quincke needles with beveled cutting tip. A procedural safety analysis was performed database multicenter, 13-week study cholinesterase...
Amyloid-β peptides, through highly sophisticated enzymatic machinery, are universally produced and released in an action potential synchronized manner into the interstitial fluids brain. Yet no native functions attributed to amyloid-β. The amyloid-β hypothesis ascribes just neurotoxicity properties build-up of soluble homomeric oligomers or fibrillar deposits. Apolipoprotein-ε4 (APOE4) allele is only confirmed genetic risk factor sporadic Alzheimer’s disease; once more it unclear how...
Death receptor‐mediated apoptosis is involved in the regulation of immune responses and maintenance immunological tolerance. FLICE‐inhibitory proteins (FLIPs) are important modulators death apoptosis. To date, FLIP family encompasses multiple members, which some reported to be antiapoptotic others pro‐apoptotic. This led us investigate activity several vitro . Concomitant with cloning various isoforms, a new unexpected member family, denoted R , was isolated from human Burkitt lymphoma...