Research Topics
Genomes and Genes | Kumar SambamurtiSummaryAffiliation: Medical University of South Carolina Country: USA Publications
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Publications
Genotoxicity in Alzheimer's disease: role of amyloidAnitha Suram
Medical University of South Carolina, Department of Neurosciences and the Center on Aging, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA
Curr Alzheimer Res 3:365-75. 2006..Further, the amalgamation of genomics and proteomics in understanding AD and therapeutic development is suggested...- A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesisKumar Sambamurti
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA
Curr Alzheimer Res 3:81-90. 2006.... - Cholesterol and Alzheimer's disease: clinical and experimental models suggest interactions of different genetic, dietary and environmental risk factorsKumar Sambamurti
Department of Physiology and Neuroscience, and Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA
Curr Drug Targets 5:517-28. 2004..The present review summarizes our current understanding of the relationship of AD pathogenesis with cholesterol, lipids and other genetic and environmental risk factors... 
Value in development of a TAPIR-like mouse monoclonal antibody to AbetaKumar Sambamurti
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
J Alzheimers Dis 14:175-7. 2008- Targets for AD treatment: conflicting messages from γ-secretase inhibitorsKumar Sambamurti
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
J Neurochem 117:359-74. 2011.... 
High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in miceLakshmi Thirumangalakudi
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
J Neurochem 106:475-85. 2008..The findings link hypercholesterolemia with cognitive dysfunction potentially mediated by increased neuroinflammation and APP processing in a non-transgenic mouse model...- Beta-secretase processing of the Alzheimer's amyloid protein precursor (APP)Laura Marlow
Medical University of South Carolina, Charleston, SC 29425, USA
J Mol Neurosci 20:233-9. 2003..We propose that the BACE complex is a better drug target than the monomer for specific inhibition of Abeta biogenesis... - Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse modelJason Lockrow
Department of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
Exp Neurol 216:278-89. 2009..This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology... - APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activityLaura Marlow
Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Suite 403, Charleston, SC 29425, USA
Biochem Biophys Res Commun 305:502-9. 2003..In addition, our studies also suggest that the presenilin partners regulate the relative levels of Abeta40 and Abeta42... - Geranylgeranyl pyrophosphate stimulates gamma-secretase to increase the generation of Abeta and APP-CTFgammaYan Zhou
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
FASEB J 22:47-54. 2008..Our results indicate that geranylgeranyl isoprenoids may be an important physiological facilitator of gamma-secretase activity that can foster production of the pathologically important Abeta42... - Amyloid precursor protein compartmentalization restricts beta-amyloid production: therapeutic targets based on BACE compartmentalizationSwetal Gandhi
Medical University of South Carolina, Charleston, SC, 29425, USA
J Mol Neurosci 24:137-43. 2004..The simplest explanation for the detection of competition between the two pathways upon phorbol ester stimulation is the partial failure of this compartmentalization by phorbol ester-induced release of secretory vesicles... - Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged ratAnn Charlotte Granholm
Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC 29425, USA
J Alzheimers Dis 14:133-45. 2008..These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology... - Beta-secretase: structure, function, and evolutionChitra Venugopal
Medical University of South Carolina, Charleston, South Carolina, USA
CNS Neurol Disord Drug Targets 7:278-94. 2008..The article also addresses the challenges in discovering a selective drug-like molecule targeting novel mechanisms of BACE-1 regulation... - Differential accumulation of secreted AbetaPP metabolites in ocular fluidsAnnamalai Prakasam
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
J Alzheimers Dis 20:1243-53. 2010..In addition, failure of free clearance from the eye may trigger retina degeneration in a manner similar to Abeta-related neurodegeneration in AD... - Human retinal pigment epithelium cells as functional models for the RPE in vivoZsolt Ablonczy
Department of Ophthalmology, Medical University of South Carolina, SEI Room 518E, 167 Ashley Avenue, Charleston, SC 29425, USA
Invest Ophthalmol Vis Sci 52:8614-20. 2011..To compare their utility as RPE models, their morphologic and functional characteristics were analyzed... - Gene structure and organization of the human beta-secretase (BACE) promoterKumar Sambamurti
Medical University of South Carolina, Charleston, South Carolina, USA
FASEB J 18:1034-6. 2004..Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis... - Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic miceJin Yu
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
J Alzheimers Dis 25:295-307. 2011..These observations suggest that a vitamin D3-enriched diet may benefit AD patients... - Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathwayHan Tun
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
J Mol Neurosci 19:31-5. 2002..This finding is consistent with the hypothesis that BACE interacts with GPI-anchored proteins that facilitate its activity possibly by chaperoning it into lipid rafts... - Insulysin cleaves the APP cytoplasmic fragment at multiple sitesChitra Venugopal
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Neurochem Res 32:2225-34. 2007..In addition, the study provides evidence for the presence of alternative CTFgamma-degrading pathways in the cell... - Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretaseZsolt Ablonczy
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
J Biol Chem 284:30177-86. 2009.... - Age-dependent loss of NGF signaling in the rat basal forebrain is due to disrupted MAPK activationBrice Williams
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA
Neurosci Lett 413:110-4. 2007..These findings might lead to development of novel treatment therapies for the memory loss associated with AD and other age-associated neurodegenerative diseases... - Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer's diseaseKumar Sambamurti
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
Neuromolecular Med 1:1-31. 2002..The present review summarizes our current understanding of APP metabolism and function and their relationship to other proteins involved in AD... - Frontiers in the pathogenesis of Alzheimer's diseaseKumar Sambamurti
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, BSB 403 Charleston, SC 29425
Indian J Psychiatry 51:S56-60. 2009..Multiple hypotheses have been proposed and the field is ready for a new generation of ideas to develop early diagnostic approaches and develop successful treatment plans... - Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degenerationAhmad Salehi
Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA
Neuron 51:29-42. 2006..Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration... - Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzymeElizabeth A Eckman
Mayo Clinic Jacksonville, Florida 32224, USA
J Biol Chem 278:2081-4. 2003.... - Taking down the unindicted co-conspirators of amyloid beta-peptide-mediated neuronal death: shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factorsDebomoy K Lahiri
Indiana University School of Medicine, Department of Psychiatry, Institute of Psychiatric Research, Indianapolis, IN 46202, USA
Curr Alzheimer Res 3:475-83. 2006.... - An increase in Abeta42 in the prefrontal cortex is associated with a reversal-learning impairment in Alzheimer's disease model Tg2576 APPsw miceJia Min Zhuo
Mayo Clinic College of Medicine, Jacksonville, FL, USA
Curr Alzheimer Res 5:385-91. 2008..These data suggest that the early emergence of reversal-learning deficits in the Tg2576 mouse may be due to the localized increase of Abeta42 in the prefrontal cortex... - Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and ironTracyAnn Perry
Section of Drug Design and Development, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
J Neurosci Res 72:603-12. 2003..Collectively, these data suggest that GLP-1 can modify APP processing and protect against oxidative injury, two actions that suggest a novel therapeutic target for intervention in Alzheimer's disease... - 17beta-estradiol reduces plasma Abeta40 for HRT-naïve postmenopausal women with Alzheimer disease: a preliminary studyLaura D Baker
Geriatric Research, Education, and Clinical Center, the VA Puget Sound Health Care System, Seattle/Tacoma, WA, USA
Am J Geriatr Psychiatry 11:239-44. 2003..This finding suggests that the hormone may serve as an Abeta-lowering agent for HRT-naïve AD women, which may, in turn, have ultimate ramifications for the progression of AD pathology... - Functional characterization of the 5' flanking region of the BACE gene: identification of a 91 bp fragment involved in basal level of BACE promoter expressionYuan Wen Ge
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA
FASEB J 18:1037-9. 2004..Changes in the activity of this region could play an important role in regulating BACE activity in neurons... - Nicotine lowers the secretion of the Alzheimer's amyloid beta-protein precursor that contains amyloid beta-peptide in ratTadanobu Utsuki
Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA
J Alzheimers Dis 4:405-15. 2002..These results suggest that within the brain, levels of total sAPP, sAPPgamma and, accordingly, Abeta are subject to cholinergic manipulation, offering therapeutic potential at the level of AbetaPP processing to decrease Abetadeposition... - The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and miceDebomoy K Lahiri
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA
J Pharmacol Exp Ther 320:386-96. 2007..Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment... - Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levelsJavier Pacheco-Quinto
Neuroscience Center of Excellence, LSU Health Science Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA
Neurobiol Dis 22:651-6. 2006..By unveiling a link between homocysteine and Abeta levels, these findings advance our understanding on the mechanisms involved in hyperhomocysteinemia as a risk factor for AD... - Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodentNigel H Greig
Laboratory of Neurosciences and Laboratory of Experimental Gerontology, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA
Proc Natl Acad Sci U S A 102:17213-8. 2005..Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease... - Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptideTada Utsuki
Department of Biochemistry and Molecular Biology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71115, USA
J Pharmacol Exp Ther 318:855-62. 2006..Translation of APP and A beta actions to mice was demonstrated with one agent. They thus represent interesting lead molecules for assessment in animal models, to define their tolerance and utility as potential AD therapeutics... - Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivoBonnie C Miller
Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas 75390 9151, USA
Proc Natl Acad Sci U S A 100:6221-6. 2003..These findings indicate that there is an inverse correlation between in vivo insulysin activity levels and brain Abeta peptide levels and suggest that modulation of insulysin activity may alter the risk for Alzheimer's disease... - An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's diseaseNigel H Greig
Drug Design and Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Curr Alzheimer Res 2:281-90. 2005..Further randomized, double-blind, placebo-controlled Phase III studies assessing the efficacy, safety/tolerability and potential disease-modifying effects of (-)-phenserine in patients with AD are currently ongoing... - Butyrylcholinesterase: an important new target in Alzheimer's disease therapyNigel H Greig
Drug Design and Development Section, Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, USA
Int Psychogeriatr 14:77-91. 2002..The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options... - A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's diseaseDebomoy K Lahiri
Department of Psychiatry and Neurology, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 4887, USA
Curr Drug Targets 4:97-112. 2003..All these current research efforts should lead to a deeper understanding of the pathobiochemical processes that occur in the AD brain in order to effectively diagnose and prevent their occurrence... - Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's diseaseDebomoy K Lahiri
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Neurobiol Aging 25:651-60. 2004..Thus, ApoE4 contributes to the pathogenesis of AD, but additional environmental risk factors will also be identified independent of ApoE and other genetic polymorphisms... - Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: a role in Alzheimer's disease?David Tweedie
Section on Drug Design and Delivery, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA
J Alzheimers Dis 10:9-16. 2006..Using subtoxic concentrations of neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples... - Differential expression of cholesterol hydroxylases in Alzheimer's diseaseJames Brown
Departments of Pharmacology and Pathology, Loyola University Medical Center, Maywood, IL 60153, USA
J Biol Chem 279:34674-81. 2004....
Research Grants
- Regulation and Cell Biology of Beta-SecretaseKumar Sambamurti; Fiscal Year: 2007..In aim 2, the effects of cholesterol, a known stimulator of beta-secretase processing, will be evaluated on the levels and activity of BACE complex. In aim 3, the basis of enhanced BACE activity in the complex will be evaluated. ..
- Cholesterol and amyloidogenesisKumar Sambamurti; Fiscal Year: 2007..These hypotheses are amenable to testing as outlined in the corresponding sections of the proposal and their study will advance our understanding of the pathogenesis of Alzheimer's disease. ..