Kumar Sambamurti

Summary

Affiliation: Medical University of South Carolina
Country: USA

Publications

  1. pmc Value in development of a TAPIR-like mouse monoclonal antibody to Abeta
    Kumar Sambamurti
    Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
    J Alzheimers Dis 14:175-7. 2008
  2. ncbi request reprint A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesis
    Kumar 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
  3. ncbi request reprint Genotoxicity in Alzheimer's disease: role of amyloid
    Anitha 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
  4. ncbi request reprint Cholesterol and Alzheimer's disease: clinical and experimental models suggest interactions of different genetic, dietary and environmental risk factors
    Kumar 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
  5. pmc Targets for AD treatment: conflicting messages from γ-secretase inhibitors
    Kumar Sambamurti
    Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurochem 117:359-74. 2011
  6. doi request reprint High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice
    Lakshmi Thirumangalakudi
    Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurochem 106:475-85. 2008
  7. ncbi request reprint 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
  8. pmc Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
    Jason 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
  9. ncbi request reprint APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity
    Laura 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
  10. pmc Geranylgeranyl pyrophosphate stimulates gamma-secretase to increase the generation of Abeta and APP-CTFgamma
    Yan Zhou
    Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    FASEB J 22:47-54. 2008

Research Grants

  1. Regulation and Cell Biology of Beta-Secretase
    Kumar Sambamurti; Fiscal Year: 2007
  2. Cholesterol and amyloidogenesis
    Kumar Sambamurti; Fiscal Year: 2007

Collaborators

Detail Information

Publications42

  1. pmc Value in development of a TAPIR-like mouse monoclonal antibody to Abeta
    Kumar Sambamurti
    Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
    J Alzheimers Dis 14:175-7. 2008
  2. ncbi request reprint A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesis
    Kumar 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
    ....
  3. ncbi request reprint Genotoxicity in Alzheimer's disease: role of amyloid
    Anitha 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...
  4. ncbi request reprint Cholesterol and Alzheimer's disease: clinical and experimental models suggest interactions of different genetic, dietary and environmental risk factors
    Kumar 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...
  5. pmc Targets for AD treatment: conflicting messages from γ-secretase inhibitors
    Kumar Sambamurti
    Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurochem 117:359-74. 2011
    ....
  6. doi request reprint High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice
    Lakshmi 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...
  7. ncbi request reprint 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...
  8. pmc Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
    Jason 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...
  9. ncbi request reprint APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity
    Laura 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...
  10. pmc Geranylgeranyl pyrophosphate stimulates gamma-secretase to increase the generation of Abeta and APP-CTFgamma
    Yan 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...
  11. ncbi request reprint Amyloid precursor protein compartmentalization restricts beta-amyloid production: therapeutic targets based on BACE compartmentalization
    Swetal 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...
  12. pmc Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat
    Ann 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...
  13. pmc Beta-secretase: structure, function, and evolution
    Chitra 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...
  14. pmc Differential accumulation of secreted AbetaPP metabolites in ocular fluids
    Annamalai 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...
  15. pmc Human retinal pigment epithelium cells as functional models for the RPE in vivo
    Zsolt 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...
  16. ncbi request reprint Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathway
    Han 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...
  17. doi request reprint Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice
    Jin 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...
  18. ncbi request reprint Insulysin cleaves the APP cytoplasmic fragment at multiple sites
    Chitra 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...
  19. ncbi request reprint Gene structure and organization of the human beta-secretase (BACE) promoter
    Kumar 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...
  20. pmc Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretase
    Zsolt Ablonczy
    Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 284:30177-86. 2009
    ....
  21. ncbi request reprint Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer's disease
    Kumar 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...
  22. pmc Age-dependent loss of NGF signaling in the rat basal forebrain is due to disrupted MAPK activation
    Brice 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...
  23. pmc Frontiers in the pathogenesis of Alzheimer's disease
    Kumar 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...
  24. ncbi request reprint Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levels
    Javier 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...
  25. ncbi request reprint Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme
    Elizabeth A Eckman
    Mayo Clinic Jacksonville, Florida 32224, USA
    J Biol Chem 278:2081-4. 2003
    ....
  26. ncbi request reprint 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 factors
    Debomoy 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
    ....
  27. ncbi request reprint An increase in Abeta42 in the prefrontal cortex is associated with a reversal-learning impairment in Alzheimer's disease model Tg2576 APPsw mice
    Jia 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...
  28. ncbi request reprint Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron
    TracyAnn 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...
  29. ncbi request reprint 17beta-estradiol reduces plasma Abeta40 for HRT-naïve postmenopausal women with Alzheimer disease: a preliminary study
    Laura 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
    ..The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Abeta40, for postmenopausal women with AD...
  30. ncbi request reprint Functional characterization of the 5' flanking region of the BACE gene: identification of a 91 bp fragment involved in basal level of BACE promoter expression
    Yuan 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...
  31. ncbi request reprint Nicotine lowers the secretion of the Alzheimer's amyloid beta-protein precursor that contains amyloid beta-peptide in rat
    Tadanobu 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...
  32. ncbi request reprint Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration
    Ahmad 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...
  33. ncbi request reprint The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice
    Debomoy 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...
  34. pmc Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent
    Nigel 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...
  35. ncbi request reprint Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptide
    Tada 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...
  36. pmc Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivo
    Bonnie 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...
  37. ncbi request reprint An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease
    Nigel 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...
  38. ncbi request reprint Butyrylcholinesterase: an important new target in Alzheimer's disease therapy
    Nigel 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...
  39. ncbi request reprint A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease
    Debomoy 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...
  40. ncbi request reprint 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...
  41. ncbi request reprint Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's disease
    Debomoy 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...
  42. ncbi request reprint Differential expression of cholesterol hydroxylases in Alzheimer's disease
    James Brown
    Departments of Pharmacology and Pathology, Loyola University Medical Center, Maywood, IL 60153, USA
    J Biol Chem 279:34674-81. 2004
    ....

Research Grants7

  1. Regulation and Cell Biology of Beta-Secretase
    Kumar 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. ..
  2. Cholesterol and amyloidogenesis
    Kumar 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. ..