Synthesis, biochemical evaluation, and molecular modeling of organophosphate-coumarin hybrids as potent and selective butyrylcholinesterase inhibitors.

A small library of new organophosphorylated warfarins and 3-benzylcoumarins were synthesized and evaluated for in vitro cholinesterase inhibition by Ellman's method. Most of the compounds were found to be selective for butyrylcholinesterase (BChE) over acetylcholinesterase (AChE), with IC values ranging from 0.363 μM to 53.

Impaired Glucose Tolerance and Reduced Plasma Insulin Precede Decreased AKT Phosphorylation and GLUT3 Translocation in the Hippocampus of Old 3xTg-AD Mice.

Several studies have demonstrated that mouse models of Alzheimer's disease (AD) can exhibit impaired peripheral glucose tolerance. Further, in the APP/PS1 mouse model, this is observed prior to the appearance of AD-related neuropathology (e.g.

Differential Fasting Plasma Glucose and Ketone Body Levels in GHRKO versus 3xTg-AD Mice: A Potential Contributor to Aging-Related Cognitive Status?

Cognitive function declines with age and appears to correlate with decreased cerebral metabolic rate (CMR). Caloric restriction, an antiaging manipulation that extends life-span and can preserve cognitive function, is associated with decreased glucose uptake, decreased lactate levels, and increased ketone body (KB) levels in the brain. Since the majority of brain nutrients come from the periphery, this study examined whether the capacity to regulate peripheral glucose levels and KB production differs in animals with successful cognitive aging (growth hormone receptor knockouts, GHRKOs) versus unsuccessful cognitive aging (the 3xTg-AD mouse model of Alzheimer's disease).

Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggests that both type 1 and type 2 diabetes are risk factors for AD-related dementia and several clinical studies have demonstrated that AD patients show alterations in peripheral glucose regulation characterized by insulin resistance (hyperinsulinemia) or hypoinsulinemia. Whether animal models of AD exhibit a pre-diabetic phenotype without additional dietary or experimental manipulation is unclear however, with contradictory data available.