Research Topics
Genomes and Genes | Huaxi XuSummaryAffiliation: The Burnham Institute Country: USA Publications
Research Grants
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Detail Information
Publications
NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegenerationYoung Don Kwak
Department of Pharmacology, University of Tennessee Health Science Center, College of Medicine, 874 Union Avenue, Memphis TN, 38163, USA
Mol Neurodegener 5:49. 2010..However the molecular signals and mechanism underlying PTEN loss are unknown...
Estrogen, beta-amyloid metabolism/trafficking, and Alzheimer's diseaseHuaxi Xu
Center for Neurosciences and Aging, Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Ann N Y Acad Sci 1089:324-42. 2006....- Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Abeta and insulin degradationAyelen Bulloj
Fundacion Instituto Leloir, IIBBA CONICET, Ave, Patricias Argentinas 435, Ciudad de Buenos Aires C1405BWE, Argentina
Mol Neurodegener 3:22. 2008..Although IDE sub-cellular localization has been well studied, the compartments relevant to Abeta degradation remain to be determined... - Intracellular trafficking of presenilin 1 is regulated by beta-amyloid precursor protein and phospholipase D1Yun Liu
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 284:12145-52. 2009..Our results clearly elucidate a physiological function of APP in regulating protein trafficking and suggest that intracellular trafficking of PS1/gamma-secretase is regulated by multiple factors, including APP and PLD1... - Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expressionYun Wu Zhang
Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 104:10613-8. 2007..Our results indicate an important role of PS/gamma-secretase-generated APP metabolite AICD in gene transcription and in EGFR-mediated tumorigenesis... - Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubulesXue Zhang
Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92037, USA
FASEB J 20:1272-4. 2006..These findings suggest a link between malfunction of PTEN and tauopathy, and imply PTEN as a therapeutic target for tauopathy... - Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesisPing Lin
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA
J Neurochem 100:1505-14. 2007..Our results suggest a novel function of calnuc in modulating the levels of APP and its proteolytic metabolites, which may further affect the patho/physiological functions of APP including AD pathogenesis... - Alteration of beta-secretase traffic by the receptor tyrosine kinase signaling pathway - a new mechanism for regulating Alzheimer's beta-amyloid productionYun-wu Zhang
Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 N. Torrey Pines Rd, La Jolla, CA 92037, USA
Cell Res 17:385-6. 2007 - Functional interaction of phosphatase and tensin homologue (PTEN) with the E3 ligase NEDD4-1 during neuronal response to zincYoung Don Kwak
Neurodegenerative Disease Program, Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 285:9847-57. 2010..This study demonstrates that NEDD4-1-mediated PTEN ubiquitination is crucial in the regulation of PI3K/Akt signaling by PTEN during the neuronal response to zinc, which may represent a common mechanism in neurodegeneration... - Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylationPing Han
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
J Neurosci 25:11542-52. 2005..We suggest that CDK5 activation, through a calcium/calpain/p25 pathway, plays a key role in neuronal excitotoxicity and represents an underlying mechanism for the physiological functions of APP... 
Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading proteaseAyelen Bulloj
Fundacion Instituto Leloir, IIBBA CONICET, Ciudad de Buenos Aires, Argentina
J Alzheimers Dis 19:79-95. 2010..Our results reinforce the relevance of functional IDE in the catabolism of extracellular Abeta...- Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcriptionYaomin Chen
Neurodegenerative Disease Research Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 106:3907-12. 2009..Our findings suggest a potentially harmful consequence of this widely prescribed antidiabetic drug when used as a monotherapy in elderly diabetic patients... - Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase componentsYun Wu Zhang
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 280:17020-6. 2005.... - Alzheimer's presenilin 1 modulates sorting of APP and its carboxyl-terminal fragments in cerebral neurons in vivoSam Gandy
Farber Institute for Neurosciences and the Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
J Neurochem 102:619-26. 2007..The chimera experiment suggests that TGN-enrichment of a beta-/gamma-secretase substrate may play an integral role in the action of mutant PS1 to elevate brain levels of Abeta42... - Molecular and cellular mechanisms for Alzheimer's disease: understanding APP metabolismYun Wu Zhang
Institute for Biomedical Research, Xiamen University, China
Curr Mol Med 7:687-96. 2007.... - Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesisJeffrey P Greenfield
Fisher Center for Research on Alzheimer s Disease and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 277:12128-36. 2002..These results suggest a novel mechanism through which 17beta-E2 may act in estrogen-responsive tissues and illustrate how altering the kinetics of the transport of a protein can influence its metabolic fate... - Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formationDongming Cai
Laboratory of Molecular and Cellular Neuroscience, and Fisher Center for Research on Alzheimer Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Proc Natl Acad Sci U S A 103:1941-6. 2006..The data indicate that overexpression of PLD1 decreases, and down-regulation of PLD1 increases, the catalytic activity, and the association of the subunits, of gamma-secretase... - Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathologyReisuke H Takahashi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
Am J Pathol 161:1869-79. 2002..This accumulation was associated with abnormal synaptic morphology, before beta-amyloid plaque pathology, suggesting that intracellular accumulation of beta-amyloid plays a crucial role in Alzheimer's disease... - Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neuronsDongming Cai
Laboratory of Molecular and Cellular Neuroscience, and Fisher Center for Research on Alzheimer Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Proc Natl Acad Sci U S A 103:1936-40. 2006..The impaired neurite outgrowth capacity in FAD mutant neurons was corrected by introducing PLD1 into these cells. The results indicate that PLD1 may represent a therapeutic target for rescuing compromised neuronal function in AD... - A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surfaceJae Yoon Leem
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Illinois 60637, USA
Neurobiol Dis 11:64-82. 2002..Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins... - Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761Yuan Luo
Departments of Biological Sciences and Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA
Proc Natl Acad Sci U S A 99:12197-202. 2002.... - Modulation of beta-amyloid metabolism by non-steroidal anti-inflammatory drugs in neuronal cell culturesLaura Gasparini
Nicox Research Institute, Bresso, Milan, Italy
J Neurochem 88:337-48. 2004..The present findings show that only a few non-selective NSAIDs possess Abeta-lowering properties and therefore have a profile potentially relevant to their clinical use in AD... - Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor proteinDongming Cai
Fisher Center for Research on Alzheimer s Disease and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 278:3446-54. 2003..These results suggest that PS1 regulation of beta APP trafficking may represent an alternative mechanism by which FAD-linked PS1 variants modulate beta APP processing... - Cholesterol retention in Alzheimer's brain is responsible for high beta- and gamma-secretase activities and Abeta productionHuaqi Xiong
Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada
Neurobiol Dis 29:422-37. 2008.... - Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxiaRuishan Wang
Laboratory of Molecular and Cellular Neuroscience, School of Life Sciences, Xiamen University, Xiamen, China
FASEB J 20:1275-7. 2006.... - Does insulin dysfunction play a role in Alzheimer's disease?Laura Gasparini
Nicox Research Institute, Via Ariosto 21, 20091 Bresso, Milan, Italy
Trends Pharmacol Sci 23:288-93. 2002..Insulin also affects the metabolism of beta-amyloid, the main constituent of AD amyloid pathology. Here, we discuss clinical and biological data that highlight potential targets for therapeutic intervention... - Presenilin 1 is required for maturation and cell surface accumulation of nicastrinJae Yoon Leem
Department of Neurobiology, Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 277:19236-40. 2002..Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex... - Improved prediction of coreceptor usage and phenotype of HIV-1 based on combined features of V3 loop sequence using random forestShungao Xu
Department of Biochemistry and Molecular Biology, Jiangsu University School of Medical Technology, Zhenjiang, Jiangsu, PR China
J Microbiol 45:441-6. 2007..Among these features, V3 polarity and four V3 sites (22, 12, 18 and 13) are first reported to have high contribution to HIV-1 biological phenotype prediction... - Chaperones increase association of tau protein with microtubulesFei Dou
Fisher Center for Research on Alzheimer's Disease, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Proc Natl Acad Sci U S A 100:721-6. 2003..Our results suggest that up-regulation of molecular chaperones may suppress formation of neurofibrillary tangles by partitioning tau into a productive folding pathway and thereby preventing tau aggregation... - Potential roles of insulin and IGF-1 in Alzheimer's diseaseLaura Gasparini
Nicox Research Institute, Via Ariosto 21, 20091 Bresso, Milan, Italy
Trends Neurosci 26:404-6. 2003..This review discusses available biological data that highlight the therapeutic potential of the insulin-IGF-1 signaling pathway in AD... - Gleevec inhibits beta-amyloid production but not Notch cleavageWilliam J Netzer
Fisher Center for Research on Alzheimer's Disease, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA
Proc Natl Acad Sci U S A 100:12444-9. 2003..The efficacy of STI571 in reducing Abeta without affecting Notch-1 cleavage may prove useful as a basis for developing novel therapies for Alzheimer's disease... - Phosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer's neurodegenerationHong Lian Li
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Proc Natl Acad Sci U S A 104:3591-6. 2007..Our findings suggest that tau phosphorylation may lead the neurons to escape from an acute apoptotic death, implying the essence of neurodegeneration seen in the AD brains and related tauopathies... - Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generationXian Zhang
Institute for Biomedical Research and School of Life Sciences, Xiamen University, Xiamen 361005, China
J Biol Chem 282:10873-80. 2007..Our results demonstrate an important role for hypoxia/HIF-1alpha in modulating the amyloidogenic processing of APP and provide a molecular mechanism for increased incidence of AD following cerebral ischemic and stroke injuries... - Presenilins and gamma-secretase inhibitors affect intracellular trafficking and cell surface localization of the gamma-secretase complex componentsHong Wang
The Fisher Center for Alzheimer's Disease Research and the Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 279:40560-6. 2004.... - Presenilins regulate the cellular level of the tumor suppressor PTENHan Zhang
Institute for Biomedical Research and School of Life Sciences, Xiamen University, 361005 Xiamen, China
Neurobiol Aging 29:653-60. 2008..Our data suggest an important role for PS in signaling pathways involving PI3K/Akt and PTEN that are crucial for physiological functions and the pathogenesis of multiple diseases... - Ubiquitin-proteasome pathway mediates degradation of APH-1Guiqiong He
Department of Psychiatry, Brain Research Center, The University of British Columbia, Vancouver, British Columbia, and Samuel Lunenfeld Research Institute, Program in Molecular Biology and Cancer, Mount Sinai Hospital, Toronto, Ontario, Canada
J Neurochem 99:1403-12. 2006..These results demonstrate that the degradation of APH-1 protein is mediated by the ubiquitin-proteasome pathway... - Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranesKulandaivelu S Vetrivel
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Illinois 60637, USA
J Biol Chem 279:44945-54. 2004..These findings are consistent with the localization of gamma-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP... - Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell cultureZe-Fen Wang
Pathophysiology Department, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
J Neurochem 98:1167-75. 2006..These results suggest that endogenously overproduced Abeta induces increased tau phosphorylation through activation of GSK-3, and that inactivation of PKC is at least one of the mechanisms involved in GSK-3 activation...
Research Grants
- Presenilins and APP in Protein TraffickingHuaxi Xu; Fiscal Year: 2010..Results of these studies will greatly facilitate our understanding of AD pathogenesis and aid in the development of therapeutics. ..
- Transcriptional Regulation of BACE and the Components of the gamma-Secretase CompHuaxi Xu; Fiscal Year: 2009..Studying transcriptional regulation of these secretase components should be instrumental for developing effective therapies for AD. ..
- Presenilins in Protein TraffickingHuaxi Xu; Fiscal Year: 2007..Aim 3 proposes to assess physiological implications of PS1 regulated axonal transport of APP in neuronal functions such as neurite outgrowth and synapse formation. ..
- Transcriptional Regulation of BACE and the Components of the gamma-Secretase CompHuaxi Xu; Fiscal Year: 2007..Studying transcriptional regulation of these secretase components should be instrumental for developing effective therapies for AD. ..
- Identifying genes in Beta-Amyloid ProductionHuaxi Xu; Fiscal Year: 2007..Specific Aim 2 is to validate and characterize the genes identified and to understand how these gene products may affect betaAPP metabolism. ..
- Transcriptional Regulation of BACE and the Components of the gamma-Secretase CompHuaxi Xu; Fiscal Year: 2010..Studying transcriptional regulation of these secretase components should be instrumental for developing effective therapies for AD. ..