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ABSTRACT: The selection of foods to eat is a complex interplay of vision, taste, smell, and texture. In addition to micro- and macronutrients, plant-based foods also contain several classes of phytochemicals. In many cases, the phytochemicals account for the various colors of foods. Although aesthetically pleasing, the color of foods may mislead consumers as to their phytochemical content, which is particularly true with regard to polyphenols. Polyphenols are a broad class of compounds with antioxidant and other health benefits. Human vision is limited to a small window (390-765 nm) of the electromagnetic spectrum. Many important phytochemicals (e.g., vitamin C) have no absorbance in this range. Therefore, the human eye cannot directly judge the vitamin C content of foods. Being able to see in the ultraviolet range allows bees to locate the pollen-rich region of flowers, whereas pit vipers locate their prey by being able to "see" them in the infrared range. Assessing the impact of phytochemicals on human health depends on several factors. Colorless phytochemicals in unprocessed foods may be lost during the cooking process because no visual guide exists to ensure their retention. The molecular structures of phytochemicals influence the extent to which they are altered by cooking processes and the methods by which they are absorbed from the gastrointestinal tract. Extensive metabolism by phase I/II enzymes and by the gut microbiome may also create compounds that the eye is never allowed to appreciate.
Advances in nutrition (Bethesda, Md.). 01/2013; 4(3):327S-334S.
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ABSTRACT: To evaluate the consequences of expression of the protein encoded by PAX3-FOXO1 (P3F) in the pediatric malignancy alveolar rhabdomyosarcoma (A-RMS), we developed and evaluated a genetically defined in vitro model of A-RMS tumorigenesis. The expression of P3F in cooperation with simian virus 40 (SV40) Large-T (LT) antigen in murine C3H10T1/2 fibroblasts led to robust malignant transformation. Using 2-dimensional-difference gel electrophoresis (2D-DIGE), we compared proteomes from lysates from cells that express P3F + LT versus from cells that express LT alone. Analysis of 2D gel spot patterns by DeCyder image analysis software indicated 93 spots that were different in abundance. Peptide mass fingerprint analysis of the 93 spots by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis identified 37 nonredundant proteins. 2D-DIGE analysis of cell culture media conditioned by cells transduced by P3F + LT versus by LT alone found 29 spots in the P3F + LT cells leading to the identification of 11 nonredundant proteins. A substantial number of proteins with potential roles in tumorigenesis and myogenesis were detected, most of which have not been identified in previous wide-scale expression studies of RMS experimental models or tumors. We validated the 2D gel image analysis findings by Western blot analysis and immunohistochemistry (IHC). Thus, the 2D-DIGE proteomics methodology described here provided an important discovery approach to the study of RMS biology and complements the findings of previous mRNA expression studies.
Journal of Proteome Research 02/2011; 10(2):624-36. · 5.11 Impact Factor
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ABSTRACT: Cell culture models of oncogenesis that use cellular reprogramming to generate a neoplastic cell from a normal cell provide one of the few opportunities to study the early stages of breast cancer development. Human mammary epithelial cells (HMECs) were induced to undergo a neoplastic transformation using defined genetic elements to generate transformed HMECs (THMECs). To identify proteins that displayed significantly different levels of abundance at three consecutive time points in oncogenesis over an 80 day period, protein extracts were analyzed by two-dimensional difference gel electrophoresis (2D-DIGE). Nine proteins were found to be significantly different in abundance: keratin 1, keratin 7, heat shock protein 4A-like, t-complex protein 1, stathmin, gelsolin, FK506 binding protein 5, ribosomal protein P0, and maspin. Keratin 7 and maspin displayed a linear down-regulation over 80 days. All of these proteins have been shown to be involved in the maintenance of a metastatic state including cytoskeletal modifications and motility. We conclude that, following neoplastic induction, THMECs display an early and progressive increase in metastatic potential. Further investigations into the function and regulatory mechanisms of these proteins will provide an unparalleled understanding of the initial states through which a breast cancer cell transitions following acquisition of the genetic abnormalities required for oncogenesis.
Journal of Proteome Research 02/2011; 10(2):447-58. · 5.11 Impact Factor
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Elsa M Janle,
Mary Ann Lila,
Michael Grannan,
Lauren Wood,
Aine Higgins,
Gad G Yousef,
Randy B Rogers, Helen Kim,
George S Jackson,
Lap Ho,
Connie M Weaver
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ABSTRACT: Grape polyphenols confer potential health benefits, including prevention of neurodegenerative diseases. To determine the absorption and tissue distribution of the complex grape polyphenol mixture, (14)C-labeled polyphenols were biosynthesized by grape cell suspension cultures, during co-incubation with radioisotopically labeled sucrose, and fractionated into polyphenolic subfractions. The pharmacokinetics and distribution of grape polyphenols into blood, brain, and peripheral interstitial fluid were determined by tracking the (14)C label. The blood peak (14)C concentration of the fractions ranged from 15 minutes to 4 hours. Absorption and tissue distribution varied greatly between fractions. Concentrations in interstitial fluid were lower than in blood. The amount of residual label in the brain at 24 hours ranged from 0.1% to 1.7% of the dose, depending on the fraction. (14)C label found in the brain tissue and brain microdialysate indicated that grape polyphenols or their metabolites are able to cross the blood-brain barrier. Using (14)C-labeled plant polyphenols it is possible to track the compounds or their metabolic products into any tissue and determine distribution patterns in spite of low concentrations. A central question regarding the potential role of dietary polyphenolics in neurodegenerative research is whether they are bioavailable in the brain. Our observations indicate that some grape-derived polyphenolics do reach the brain, which suggests their potential value for applications in neurodegenerative disorders.
Journal of medicinal food 08/2010; 13(4):926-33. · 1.39 Impact Factor
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ABSTRACT: This summary addresses the progress and limitations of existing research on the physiologic properties of the isoflavone daidzein metabolite equol. Previous research demonstrating that physiological equol is its S-enantiomer has led to the preparation of S-(-)equol-enriched products formed by the bacterial fermentation of soy germ. Although this product has interesting properties as described in this workshop, the following important issues must be addressed: 1) the product should be evaluated against a preparation containing an equal amount of pure S-(-)equol to determine whether other components resulting from the fermentation are contributing to the physiological effects; 2) evaluation of the cellular mechanisms of S-(-)equol using cell culture methods should be conducted at concentrations consistent with those encountered physiologically (in the nmol/L range) and in several cell lines representing a target tissue; and 3) in follow-up studies in animal models and in human clinical trials, standardized preparations of S-(-)equol should be made available. Research opportunities now exist to determine whether equol's apparent effects on menopausal symptoms (hot flashes, sleep disturbances, bone health) in equol producers can be extended to equol nonproducers. It will be important to ensure that such research is not complicated by cultural differences, differences in lifetime exposure to soy products, experimental techniques, and other variables. Further areas of research that would benefit from the availability of S-(-)equol preparations include its use in skin care (either as an antioxidant or as an estrogen receptor agonist) and in the treatment of brain injury as well as postmenopausal cognitive decline.
Journal of Nutrition 07/2010; 140(7):1390S-4S. · 3.92 Impact Factor
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ABSTRACT: Bioactive compounds in botanicals may be beneficial in preventing age-related neurodegenerative diseases, but for many compounds conventional methods may be inadequate to detect if these compounds cross the blood brain barrier or to track the pharmacokinetics in the brain. By combining a number of unique technologies it has been possible to utilize the power of AMS to study the pharmacokinetics of bioactive compounds in the brain at very low concentrations. (14)C-labeled compounds can be biosynthesized by plant cell suspension cultures co-incubated with radioisotopically-labeled sucrose and isolated and separated into a series of bioactive fractions.To study the pharmacokinetics and tissue distribution of (14)C labeled plant polyphenols, rats were implanted with jugular catheters, subcutaneous ultrafiltration probes and brain microdialysis probes. Labeled fractions were dosed orally. Interstitial fluid (ISF) and brain microdialysate samples were taken in tandem with blood samples. It was often possible to determine (14)C in blood and ISF with a β-counter. However, brain microdialysate samples (14)C levels on the order of 10(7) atoms/sample required AMS technology. The Brain Microdialysate(AUC)/Serum(AUC) ranged from .021- to .029, with the higher values for the glycoside fractions. By using AMS in combination with traditional methods, it is possible to study uptake by blood, distribution to ISF and determine the amount of a dose which can reach the brain and follow the pharmacokinetics in the brain.
Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms 04/2010; 268(7-8):1313-1316. · 1.21 Impact Factor
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ABSTRACT: The Purdue-UAB Botanicals Research Center for Age Related Disease uses multidisciplinary and innovative technologies to investigate the bioavailability of bioactive polyphenolic constituents from botanicals and their relationship to human health. Many age-related diseases are associated with oxidative stress and tissue damage. One of the research goals of the Purdue-UAB Center is to investigate the bioavailability of bioactive natural compounds from a complex botanical mixture to the organ affected by the disease, determine the uptake and metabolism of these compounds and relate these data to a protective mechanism. Equally important is to screen commercially available botanicals for their safety and efficacy. The central aims of the Center include the investigation of botanicals and their relationship to bone antiresorptive capacity, cognitive function, vascular effects, and cancer prevention.
Pharmaceutical Biology 08/2009; 47(8):768-773. · 0.88 Impact Factor
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ABSTRACT: Proanthocyanidin rich plant extracts derived from grape seed extract (GSE), hawthorn and cranberry are on markets for their preventive effects against cardiovascular diseases and uroinfections in woman. However, the importance of these health beneficial effects of these botanicals remains elusive due to incomplete understanding of uptake, metabolism and bioavailability of proanthocyanidins in vivo. In the present study rats were given GSE orally (300 mg/kg, twice a day) and blood and urine were collected over a 24 h period. Monomeric catechins and their methylated metabolites, and proanthocyanidins up to trimers were detected in blood samples treated with GSE using LC-MS/MS operating in the multiple reaction monitoring (MRM) mode. A new tetramethylated metabolite of dimeric proanthocyanidin (m/z 633) in GSE-treated urine was tentatively identified. Using LC-MS/MS, (+)-catechin and (-)-epicatechin were identified in the brain conclusively. These data suggested that GSE catechins cross the blood brain barrier and may be responsible for the neuroprotective effects of GSE.
Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2009; 16(2-3):233-43. · 2.17 Impact Factor
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ABSTRACT: MS, with or without pre-analysis peptide fractionation, can be used to decipher the residues on proteins where oxidative modifications caused by peroxynitrite, singlet oxygen or electrophilic lipids have occurred. Peroxynitrite nitrates tyrosine and tryptophan residues on the surface of actin. Singlet oxygen, formed by the interaction of UVA light with tryptophan, can oxidize neighbouring cysteine, histidine, methionine, tyrosine and tryptophan residues. Dose-response inactivation by 4HNE (4-hydroxynonenal) of hBAT (human bile acid CoA:amino acid N-acyltransferase) and CKBB (cytosolic brain isoform of creatine kinase) is associated with site-specific modifications. FT-ICR (Fourier-transform ion cyclotron resonance)-MS using nanoLC (nano-liquid chromatography)-ESI (electrospray ionization)-MS or direct-infusion ESI-MS with gas-phase fractionation identified 14 4HNE adducts on hBAT and 17 on CKBB respectively. At 4HNE concentrations in the physiological range, one member of the catalytic triad of hBAT (His362) was modified; for CKBB, although all four residues in the active site that were modifiable by 4HNE were ultimately modified, only one, Cys283, occurred at physiological concentrations of 4HNE. These results suggest that future in vivo studies should carefully assess the critical sites that are modified rather than using antibodies that do not distinguish between different modified sites.
Biochemical Society Transactions 11/2008; 36(Pt 5):1037-44. · 3.71 Impact Factor
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ABSTRACT: Rat mammary gland proteomes at day 21 (prepubertal) and day 50 (late puberty) were compared by 2D difference gel electrophoresis. Two-hundred fifty-one spots were significantly different ( p < 0.05) in abundance. Peptide mass fingerprint analysis of a subset of these proteins identified two significantly over-represented classes including structural and blood proteins (increased), and metabolism-relevant proteins (reduced) in day 50 relative to day 21 glands. This is a first report of mammary gland proteome differences at these important breast cancer-relevant time-points.
Journal of Proteome Research 09/2008; 7(11):4638-50. · 5.11 Impact Factor
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Poonam Sarkar,
Shubhashish Sarkar,
Vani Ramesh, Helen Kim,
Stephen Barnes,
Anil Kulkarni,
Joseph C Hall,
Bobby L Wilson,
Renard L Thomas,
Neal R Pellis,
Govindarajan T Ramesh
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ABSTRACT: Exposure to altered microgravity during space travel induces changes in the brain and these are reflected in many of the physical behavior seen in the astronauts. The vulnerability of the brain to microgravity stress has been reviewed and reported. Identifying microgravity-induced changes in the brain proteome may aid in understanding the impact of the microgravity environment on brain function. In our previous study we have reported changes in specific proteins under simulated microgravity in the hippocampus using proteomics approach. In the present study the profiling of the hypothalamus region in the brain was studied as a step towards exploring the effect of microgravity in this region of the brain. Hypothalamus is the critical region in the brain that strictly controls the pituitary gland that in turn is responsible for the secretion of important hormones. Here we report a 2-dimensional gel electrophoretic analysis of the mouse hypothalamus in response to simulated microgravity. Lowered glutathione and differences in abundance expression of seven proteins were detected in the hypothalamus of mice exposed to microgravity. These changes included decreased superoxide dismutase-2 (SOD-2) and increased malate dehydrogenase and peroxiredoxin-6, reflecting reduction of the antioxidant system in the hypothalamus. Taken together the results reported here indicate that oxidative imbalance occurred in the hypothalamus in response to simulated microgravity.
Neurochemical Research 06/2008; 33(11):2335-41. · 2.24 Impact Factor
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ABSTRACT: The Purdue-University of Alabama Botanicals Research Center for Age Related Disease joins novel technologies to study the bioavailability of bioactive polyphenolic constituents and their relation to health. Many diseases that manifest with age relate to oxidative stress and tissue damage. Our goal is to follow the fate of bioactive constituents from a complex mixture to the organ affected by the disease and relate that to a protective mechanism. Equally important is to screen commercially available botanicals for their efficacy and safety. Botanicals and their relation to bone antiresorptive capacity, cognitive function, vascular effects, and cancer are principal themes in our center.
American Journal of Clinical Nutrition 03/2008; 87(2):493S-7S. · 6.67 Impact Factor
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ABSTRACT: This chapter describes protocols for two-dimensional (2D) gel electrophoresis (isoelectric focusing [IEF] followed by sodium-dodecyl
sulfate (SDS)-polyacrylamide gel electrophoresis [PAGE]), staining of gels with the fluorescent dye Sypro Ruby, 2D gel image
analysis, peptide mass fingerprint (PMF) analysis using matrix-assisted laser desorption ionization (MALDI)-time-of-flight
(TOF) mass spectrometry (MS), liquid chromatography (LC)-tandem mass spectrometry (MS/MS), Western blot analysis of protein
oxidations, and mass spectrometric mapping of sites of protein oxidations. Many of these methods were used to identify proteins
affected in rat brain following ingestion of grape seed extract (GSE), a dietary supplement touted for anti-oxidant activity.
Although beneficial actions in cell and animal models of chronic disease have been described for GSE, it has not been shown
whether specific proteins were affected, or the nature of the effects. Applying 2D gel proteomics technology allowed discovery
of proteins targeted by GSE without a priori knowledge of which one(s) might be affected. The newer 2D blue native (BN) electrophoresis methodology, which resolves protein
complexes in a nondenaturing first dimension and then the components of these complexes in a denaturing second dimension,
is discussed as a complementary approach. Analysis of protein oxidations and protein-protein interactions have special relevance
to aging-related research, since oxidative stress and altered protein interactions may be at the heart of aging-related diseases.
Finally, quality control issues related to implementation of high throughput technologies are addressed, to underscore the
importance of minimizing bias and randomizing human and technical error in generating large datasets that are expensive and
time-consuming to repeat.
Key WordsAging–2D gels–electrophoresis–neuroprotection–neurodegeneration–grape seed–anti-oxidant–MALDI-TOF–LC-MS/MS–mass spectrometry–isoelectric focusing–oxyblot–quality control–blue native gels
02/2008: pages 349-391;
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ABSTRACT: Creatine kinase reversibly catalyzes the transfer of the high-energy phosphoryl group from phosphocreatine to MgADP for rapid regeneration of ATP. It is hypothesized that factors which perturb creatine kinase activity, such as reactive oxygen species resulting from oxidative stress, could have a major role in the pathogenesis of diseases, particularly in the brain, where the level of ATP utilization is high. The reactive aldehyde 4-hydroxy-2-nonenal is a major secondary product of lipid peroxidation caused by oxidative stress; the levels of both free and protein-bound 4-hydroxy-2-nonenal are increased in Alzheimer's disease brain. Preliminary reports indicated that creatine kinase had lower activity in Alzheimer's disease brain. In this study, we investigated the structural and functional consequences of reacting the cytosolic brain isoform of creatine kinase with 4-hydroxy-2-nonenal at pathophysiologically relevant concentrations of 4-hydroxy-2-nonenal (10-300 microM). Dose-dependent reduction of enzyme activity was observed and, for the first time, correlated with 4-hydroxy-2-nonenal adduct formation on specific amino acid residues, including the active site residues His66, His191, Cys283, and His296 as determined by Fourier transform-ion cyclotron resonance mass spectrometry.
Chemical Research in Toxicology 10/2007; 20(9):1260-8. · 3.78 Impact Factor
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ABSTRACT: An important characteristic of tumors is that they at some point in their development overcome the surveillance of the immune system. Tumors secrete exosomes, multivesicular bodies containing a distinct set of proteins that can fuse with cells of the circulating immune system. Purified exosomes from TS/A breast cancer cells, but not non-exosomal fractions, inhibit (at concentrations of nanograms per ml protein) IL-2-induced natural killer (NK) cell cytotoxicity. The dietary polyphenol, curcumin (diferuloylmethane), partially reverses tumor exosome-mediated inhibition of natural killer cell activation, which is mediated through the impairment of the ubiquitin-proteasome system. Exposure of mouse breast tumor cells to curcumin causes a dose-dependent increase in ubiquitinated exosomal proteins compared to those in untreated TS/A breast tumor cells. Furthermore, exosomes isolated from tumor cells pretreated with curcumin have a much attenuated inhibition of IL-2 stimulated NK cell activation. Jak3-mediated activation of Stat5 is required for tumor cytotoxicity of IL-2 stimulated NK cells. TS/A tumor exosomes strongly inhibit activation of Stat5, whereas the tumor exosomes isolated from curcumin-pretreated tumor cells have a lowered potency for inhibition of IL-2 stimulated NK cell cytotoxicity. These data suggest that partial reversal of tumor exosome-mediated inhibition of NK cell tumor cytotoxicity may account for the anti-cancer properties of curcumin.
Biochimica et Biophysica Acta 08/2007; 1773(7):1116-23. · 4.66 Impact Factor
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ABSTRACT: This chapter describes protocols for two-dimensional (2D) gel electrophoresis (isoelectric focusing [IEF] followed by sodium-dodecyl sulfate (SDS)-polyacrylamide gel electro-phoresis [PAGE]), staining of gels with the fluorescent dye Sypro Ruby, 2D gel image analysis, peptide mass fingerprint (PMF) analysis using matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF) mass spectrometry (MS), liquid chromatography (LC)-tandem mass spectrometry (MS/MS), Western blot analysis of protein oxidations, and mass spectrometric mapping of sites of protein oxidations. Many of these methods were used to identify proteins affected in rat brain following ingestion of grape seed extract (GSE), a dietary supplement touted for anti-oxidant activity. Although beneficial actions in cell and animal models of chronic disease have been described for GSE, it has not been shown whether specific proteins were affected, or the nature of the effects. Applying 2D gel proteomics technology allowed discovery of proteins targeted by GSE without a priori knowledge of which one(s) might be affected. The newer 2D blue native (BN) electrophoresis methodology, which resolves protein complexes in a nondenaturing first dimension and then the components of these complexes in a denaturing second dimension, is discussed as a complementary approach. Analysis of protein oxidations and protein-protein interactions have special relevance to aging-related research, since oxidative stress and altered protein interactions may be at the heart of aging-related diseases. Finally, quality control issues related to implementation of high throughput technologies are addressed, to underscore the importance of minimizing bias and randomizing human and technical error in generating large datasets that are expensive and time-consuming to repeat.
Methods in molecular biology (Clifton, N.J.) 02/2007; 371:349-91.
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ABSTRACT: Normal aging is often associated with a decline in learning and memory functions. This decline is manifested to a much greater extent in Alzheimer's disease. Recent studies have indicated statins, a class of cholesterol-lowering drugs, as a potential therapy for Alzheimer's disease. Our objective was to determine whether administering a statin drug (simvastatin) would protect against the development of behavioral deficits in an established mouse model of Alzheimer's disease.
Tg2576 mice and their nontransgenic littermates were treated with simvastatin and assessed by behavioral tests and biochemical analyses.
Simvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. Moreover, levels of amyloid beta protein in the brains of treated mice did not differ from those of untreated mice. Simvastatin treatment was associated with increased expression levels of protein kinase B (Akt) and endothelial nitric oxide synthase in the mouse brain.
Our findings demonstrate that the effects of simvastatin on learning and memory are independent of amyloid beta protein levels. The mechanisms by which simvastatin exerts its beneficial effects may be related to modulation of signaling pathways in memory formation.
Annals of Neurology 01/2007; 60(6):729-39. · 11.09 Impact Factor
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ABSTRACT: Emerging evidence indicates that cholesterol metabolism affects the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) is obligatory in maintaining cholesterol homeostasis in the periphery. To investigate the role of LDLR in the development of AD-like behavior and pathology, Tg2576 mice, a well-characterized transgenic mouse model of AD, with different genotypes of LDLR were generated. Here we show that LDLR-deficient Tg2576 mice developed hypercholesterolemia and age-dependent cerebral beta-amyloidosis. Before the manifestation of amyloid-beta (Abeta) deposition, these mice displayed hyperactivity, reduced anxiety, and impaired spatial learning regardless of LDLR genotypes. After the manifestation of Abeta deposition, LDLR-deficient Tg2576 mice showed more spatial learning deficits than LDLR-intact Tg2576 mice. Although LDLR genotypes did not affect the expression level of the amyloid-beta precursor protein transgene, there was a significant increase in Abeta deposition accompanied with an increase of apoE expression in LDLR-deficient Tg2576 mice. Our results suggest that the LDLR plays a role in the development of Alzheimer-type learning impairment and amyloidosis and can be a novel therapeutic target for AD.
Neurobiology of aging 12/2006; 27(11):1632-43. · 5.94 Impact Factor
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ABSTRACT: Objective
Normal aging is often associated with a decline in learning and memory functions. This decline is manifested to a much greater extent in Alzheimer's disease. Recent studies have indicated statins, a class of cholesterol-lowering drugs, as a potential therapy for Alzheimer's disease. Our objective was to determine whether administering a statin drug (simvastatin) would protect against the development of behavioral deficits in an established mouse model of Alzheimer's disease.Methods
Tg2576 mice and their nontransgenic littermates were treated with simvastatin and assessed by behavioral tests and biochemical analyses.ResultsSimvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. Moreover, levels of amyloid β protein in the brains of treated mice did not differ from those of untreated mice. Simvastatin treatment was associated with increased expression levels of protein kinase B (Akt) and endothelial nitric oxide synthase in the mouse brain.InterpretationOur findings demonstrate that the effects of simvastatin on learning and memory are independent of amyloid β protein levels. The mechanisms by which simvastatin exerts its beneficial effects may be related to modulation of signaling pathways in memory formation. Ann Neurol 2006;60:729–739
Annals of Neurology 11/2006; 60(6):729 - 739. · 11.09 Impact Factor
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ABSTRACT: Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (Abeta) reduces Abeta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of anti-Abeta F(ab')(2) antibodies also induces clearance of amyloid plaques in AD mouse models, we have tested a novel gene therapy modality where an adeno-associated virus (AAV) encoding anti-Abeta single-chain antibody (scFv) is injected into the corticohippocampal regions of AD mouse models. One year after injection, expression of scFv was readily detectable in the neurons of the hippocampus without discernible neurotoxicity. AD mouse models subjected to AAV injection had much less amyloid deposits at the injection sites than the mouse models subjected to PBS injection. Because the scFv lacks the Fc portion of the immunoglobulin molecule, this modality may be a feasible solution for AD without eliciting inflammation.
Neurobiology of Disease 10/2006; 23(3):502-11. · 5.40 Impact Factor
