A5005439086- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Pesticide Exposure and Toxicity
- Neurotransmitter Receptor Influence on Behavior
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Chemical synthesis and alkaloids
- Neurological disorders and treatments
- Regulation of Appetite and Obesity
- Alzheimer's disease research and treatments
- Neuroscience and Neural Engineering
- Biochemical Analysis and Sensing Techniques
- Genetic Neurodegenerative Diseases
- Virus-based gene therapy research
- Medicinal Plants and Neuroprotection
- Forensic Toxicology and Drug Analysis
- Adipose Tissue and Metabolism
- Botulinum Toxin and Related Neurological Disorders
- Cannabis and Cannabinoid Research
Mayo Clinic
2011-2020
WinnMed
2009-2020
Mayo Clinic in Florida
2013-2017
Mayo Clinic in Arizona
1992-2017
Minnesota Oncology
2016
Ottawa Hospital
2016
Ottawa Hospital Research Institute
2016
University of Minnesota Medical Center
2016
University of Minnesota
2016
University of Rochester
1994-2008
Abstract: We have described recently an acetylcholinesterase (AChE) knockout mouse. While comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we found that extraction buffers containing Triton X‐100 strongly inhibited mouse BChE activity. In contrast, with Tween 20 caused no inhibition BChE. Conventional techniques grossly underestimated activity by up to 15‐fold. buffer, intestine, serum, lung, liver, heart had higher than Only brain in +/+ mice. These findings...
We report highly potent, selective, and low cost bifunctional acetylcholinesterase (AChE) inhibitors developed by our two-step prototype optimization strategy utilizing computer modeling of ligand docking with target proteins: 1) identify affinity sites normally missed x-ray crystallography; 2) design analogs capable simultaneous binding at the computer-determined site x-ray-identified high site. Applying this to 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug for Alzheimer's disease, we...
Rapid axonal transport was studied by several methods in rats with serum glucose levels above 300 mg/dl as a result of treatment streptozotocin (45–50 mg/kg) 3 days, 1 wk, 4 8 or mo earlier. With untreated age-matched controls, rapid anterograde the sciatic nerves diabetic appeared entirely normal. Statistically significant differences were never observed between experimental and control basal content acetylcholinesterase (AChE) dopamine-β-hydroxylase (DBH) activity rate accumulation these...
Significance Butyrylcholinesterase (BChE), a common plasma enzyme, has been known for decades but its real physiological roles are just beginning to emerge. Although BChE eliminates the neurotransmitter acetylcholine, it is not vital locomotion, cognition, or other cholinergic functions. Nevertheless, we now find that circulating large impact on aggressive behavior in mice attributable ability inactivate ghrelin, peptide hormone involved hunger, feeding, and stress. A key observation was...
To address the problem of acute cocaine overdose, we undertook molecular engineering butyrylcholinesterase (BChE) as a hydrolase so that modest doses could be used to accelerate metabolic clearance this drug. Molecular modeling BChE complexed with suggested inefficient hydrolysis (<i>k</i><sub>cat</sub> = 4 min<sup>−1</sup>) involves rotation toward catalytic triad, hindered by Tyr332. eliminate rotational hindrance and retain substrate affinity, introduced two amino acid substitutions...
Abstract: Previous observations from several groups suggest that acetylcholinesterase (AChE) may have a role in neural morphogenesis, but not solely by virtue of its ability to hydrolyze acetylcholine. We tested the possibility AChE influences neurite outgrowth nonenzymatic ways. With this aim, antisense oligonucleotides were used decrease levels transiently, and N1E.115 cell lines engineered for permanently altered protein expression. Cells stably transfected with sense cDNA construct...
Abstract Axoplasmic transport of dopamine‐β‐hydroxylase (DBH), a marker enzyme for catecholamine storage vesicles, was studied in sympathetic nerves the rat. At 24 h after ligation sciatic nerve, there marked accumulation DBH activity first 3 mm proximal to ligature. Immediately distal ligature, slight took place. Accumulation ligature linear function time at least 6 h; velocity calculated as 4.6 mm/h. Local application 1 ·l 0.1 M colchicine, caused rapid increase superior cervical ganglia....
An apparatus was devised which utilizes local cooling to reversibly interrupt the axonal transport of dopamine-beta-hydroxylase (DBH) in rabbit sciatic nerves vitro. Lowering temperature a short region nerve between 1 and 3 degrees C, while keeping remainder at 37 caused DBH activity accumulate proximal cooled region. This accumulation evident after 0.5 hr increased nearly linear fashion with time for about hr. The cooling-induced interruption rapidly reversed when were rewarmed C. Upon...
We have raised polyclonal antibodies (N6-28, L211-226, L371-384, and C590-607) against peptides corresponding to hydrophilic sequences of the human norepinephrine transporter (hNET). The antisera immunoprecipitated [<sup>35</sup>S]Met-labeled hNET. Antiserum directed a sequence putative second (large) extracellular loop hNET, also dopamine transporter. Antisera N6-28 C590-607, hNET peptide region N C termini, respectively, recognized 58-kDa protein from transfected COS-7 cells expressing...
Ghrelin is the only orexigenic hormone known to stimulate food intake and promote obesity insulin resistance. We recently showed that plasma ghrelin controlled by butyrylcholinesterase (BChE), which has a strong impact on feeding weight gain. BChE knockout (KO) mice are prone high-fat diet, but hepatic gene transfer rescues normal However, these lack brain still develop hyperinsulinemia resistance, suggesting essential interactions between within brain. To test hypothesis we used four...