Learn More
Embryonic stem (ES) cells have been established as permanent lines of undifferentiated pluripotent cells from early mouse embryos. ES cells provide a unique system for the genetic manipulation and the creation of knockout strains of mice through gene targeting. By cultivation in vitro as 3D aggregates called embryoid bodies, ES cells can differentiate into(More)
Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor(More)
The identification of signals that regulate pluripotentiality and self-renewal is fundamental to the understanding of stem cell biology. To quantify the functionally active genome of pluripotent R1 embryonic stem (ES) cells, we used the method of serial analysis of gene expression (SAGE) to sequence a total of 140,313 SAGE tags. Of 44,569 unique(More)
An explosion in the incidence of neurodegenerative diseases, particularly Alzheimer's disease (AD), is predicted in coming decades. Hence, the need to devise and assess new treatment strategies has never been more acute. AD, although an irreversible and progressive disorder, is currently treated with palliative, symptomatic therapy: primarily with(More)
Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (GLP-1R) on human neuroblastoma SH-SY5Y(More)
Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-α (TNF-α), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to be a master regulator of cellular cascades that control a number of(More)
Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF)-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide,(More)
AIMS To identify the cytochrome P450 (CYP) isoform(s) responsible for the formation of the primary metabolite of ziprasidone (ziprasidone sulphoxide), to determine the kinetics of its formation and to predict possible drug interactions by investigating CYP isoform inhibition in an in vitro study. METHODS In vitro metabolism of [14C]-ziprasidone was(More)
One of the main hallmarks of Alzheimer's disease (AD) is the brain deposition of senile plaques made up of toxic amyloid beta-peptide (Abeta), which is derived from a larger protein called the beta-amyloid precursor protein (APP). Both APP processing and cholinesterase activity are affected in the AD brain, but, yet, cholinesterase inhibitors (ChEI) remain(More)
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1(More)