Ectopic lipid accumulation, the deposition of lipids in lean tissue, is linked to type 2 diabetes through an association with insulin resistance. It occurs when adipose tissue fails to meet lipid storage needs and there is lipid spillover into tissues not equipped to store them. Ectopic lipid contributes to organ dysfunction because lipids can interfere with insulin signaling and other signaling pathways.
View Article and Find Full Text PDFResveratrol is a small molecule produced by various plants with a remarkable range of beneficial functions in animals. One of these is stimulating signaling pathways in adipose tissue that protect against obesity. Unfortunately, resveratrol suffers from poor bioavailability that inhibits its accumulation in target tissues, including fat, thus hindering the realization of its therapeutic potential.
View Article and Find Full Text PDFUnderlying metabolic disease is poor adipose tissue function characterized by impaired glucose tolerance and low expression of health promoting adipokines. Currently, no treatments specifically target the adipose tissue and we are investigating polymer scaffolds for localized drug delivery as a therapeutic platform. In this work we implanted porous poly(lactide-co-glycolide) scaffolds into the epididymal fat of mice.
View Article and Find Full Text PDFAs biomaterial therapies emerge to address adipose tissue dysfunction that underlies metabolic disease, the immune response to these systems must be established. As a potential therapy, we are investigating resveratrol delivery from porous poly(lactide- co-glycolide) scaffolds designed to integrate with adipose tissue. Resveratrol was selected for its ability to protect mice and primates from high fat diet and broad anti-inflammatory properties.
View Article and Find Full Text PDFAmyloid-beta (Abeta) accumulates in several types of retinal degeneration and in Alzheimer's disease (AD), but its source has been unclear. We detected the neuronal 695 amino acid form of amyloid-beta protein precursor (AbetaPP) in the normal retina and AbetaPP751 in the retinal pigment epithelium (RPE) and anterior eye tissues. Similar to the brain, alpha- and beta-secretases cleaved AbetaPP to soluble derivatives (sAbetaPP) alpha or beta and membrane-bound C-terminal fragments alpha or beta in the retina and RPE.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a complex neurological disorder resulting from both genetic and environmental factors with the latter being particularly important for the sporadic form of the disease. As such, diets rich in saturated fatty acids and alcohol, and deficient in antioxidants and vitamins appear to promote the onset of the disease, while diets rich in unsaturated fatty acids, vitamins, antioxidants, and wine likely suppress its onset. In addition, evidence suggests that diets rich in polyphenols and some spices suppress the onset of AD by scavenging free radicals and preventing oxidative damage.
View Article and Find Full Text PDFWet age-related macular degeneration (AMD) attacks the integrity of the retinal pigment epithelium (RPE) barrier system. The pathogenic process was hypothesized to be mediated by vascular endothelial growth factor (VEGF) and antagonized by pigment epithelium-derived factor (PEDF). To dissect these functional interactions, monolayer cultures of RPE cells were established, and changes in transepithelial resistance were evaluated after administration of PEDF, placenta growth factor (VEGF-R1 agonist), and VEGF-E (VEGF-R2 agonist).
View Article and Find Full Text PDFDown syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals.
View Article and Find Full Text PDFThe medial temporal lobe-dependent memory loss associated with Alzheimer's disease (AD) is often accompanied by a loss of prefrontal cortex-dependent cognitive domains that fall under the broad category of executive function. In this study, we examined the relationship between one type of prefrontal-dependent executive function, discrimination reversal-learning, and levels of the amyloid beta protein (Abeta) of 40 and 42 residues in a transgenic mouse model (Tg2576) of the over-expression of the familial AD mutant form of the amyloid precursor protein (APPsw). Tg2576 and their non-transgenic (NTg) littermates were assessed at 3 and 6 months of age when there is little to no amyloid plaque deposition.
View Article and Find Full Text PDFWith the ever-increasing population of aged individuals at risk of developing Alzheimer's disease (AD), there is an urgent need for a sensitive, specific, non-invasive, and diagnostic standard. The majority of efforts have focused on auto-antibodies against amyloid-beta (Abeta) protein, both as a potential treatment, and a reliable biomarker of AD pathology. Naturally occurring antibodies against Abeta are found in the CSF and plasma of patients with AD as well as healthy control subjects.
View Article and Find Full Text PDFRecent findings suggest that hypercholesterolemia may contribute to the onset of Alzheimer's disease-like dementia but the underlying mechanisms remain unknown. In this study, we evaluated the cognitive performance in rodent models of hypercholesterolemia in relation to neuroinflammatory changes and amyloid precursor protein (APP) processing, the two key parameters of Alzheimer's disease pathogenesis. Groups of normal C57BL/6 and low density lipoprotein receptor (LDLR)-deficient mice were fed a high fat/cholesterol diet for an 8-week period and tested for memory in a radial arm maze.
View Article and Find Full Text PDFCleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases results in generation of the amyloid-beta protein (Abeta), which is characteristically deposited in the brain of Alzheimer's disease patients. Inhibitors of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase (the statins) reduce levels of cholesterol and isoprenoids such as geranylgeranyl pyrophosphate (GGPP). Previous studies have demonstrated that cholesterol increases and statins reduce Abeta levels mostly by regulating beta-secretase activity.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a complex neurodegenerative disorder pathologically identified by the presence of extracellular senile plaques (SP) with a proteinaceous core composed of aggregates of the amyloid peptide (Abeta) and intracellular aggregates of the microtubule-associated protein tau (tau) as neurofibrillary tangles (NFTs). These hallmarks consist of abnormally folded proteinaceous components that are believed to be neurotoxic in AD. The mechanisms of toxicity remain unclear although oxidative stress and inflammation are implicated as mediators of the toxicity and these lesions, in turn, are known to damage cellular components including proteins, lipids in the membrane and DNA.
View Article and Find Full Text PDFThe amyloid hypothesis has dominated the thinking in our attempts to understand, diagnose and develop drugs for Alzheimer's disease (AD). This article presents a new hypothesis that takes into account the numerous familial AD (FAD) mutations in the amyloid precursor protein (APP) and its processing pathways, but suggests a new perspective beyond toxicity of forms of the amyloid beta-peptide (Abeta). Clearly, amyloid deposits are an invariable feature of AD.
View Article and Find Full Text PDFOur preliminary study shows that an oral administration of an aqueous extract of Casearia esculenta, an indigenous antidiabetic plant popularly used in South India for diabetes mellitus, lowers blood glucose level under normal and glucose load conditions, and in streptozotocin (STZ)-induced diabetes in rats. The study was further undertaken to evaluate the antioxidant potential of C. esculenta in STZ diabetic rats.
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