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Genomes and Genes | Yadong HuangSummaryAffiliation: University of California Country: USA Publications
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Publications
Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and potential therapeutic strategiesYadong Huang
Gladstone Institute of Neurological Disease, University of California, San Francisco, 1650 Owens Street, San Francisco, CA 94158, USA
Curr Opin Drug Discov Devel 9:627-41. 2006..Thus, multiple molecular and cellular mechanisms should be considered in developing anti-AD drugs that target apoE4...
Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neuronsY Huang
Gladstone Institute of Neurological Disease, P O Box 419100, San Francisco, CA 94141 9100, USA
Proc Natl Acad Sci U S A 98:8838-43. 2001....
Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's diseaseYadong Huang
the Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158, USA
Trends Mol Med 16:287-94. 2010....- Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseasesYadong Huang
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
Curr Opin Lipidol 21:337-45. 2010..The purpose of this review is to provide insights into recent advances in mechanisms linking apolipoprotein (apo) E isoforms to cardiovascular and neurological diseases... - Apolipoprotein E and Alzheimer diseaseYadong Huang
Gladstone Institute of Neurological Disease, Department of Pathology, University of California, San Francisco, CA, USA
Neurology 66:S79-85. 2006..Thus, multiple molecular and cellular mechanisms should be considered when anti-AD drugs are developed based on apoE studies... - Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer's disease: lessons from ApoE mouse modelsYadong Huang
Gladstone Institute of Neurological Disease, Department of Pathology, University of California, San Francisco, CA 94158, USA
Biochem Soc Trans 39:924-32. 2011..They also provide useful tools for discovery and development of drugs targeting apoE4's detrimental effects... - Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's diseaseYadong Huang
Gladstone Institute of Neurological Disease, Gladstone Institute of Cardiovascular Disease, and the Department of Pathology, University of California, San Francisco, CA 94141 9100, USA
J Mol Neurosci 23:189-204. 2004..Some of these mechanisms might be suitable targets for the development of new treatments for AD... - Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zincFaith M Harris
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 279:44795-801. 2004..Thus, increased tau phosphorylation in apoE4 transgenic mice was associated with Erk activation and could be modified by zinc, suggesting that apoE4 and zinc act in concert to contribute to the pathogenesis of AD... - Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic miceWalter J Brecht
Gladstone Institute of Neurological Disease, San Francisco, California 94141 9100, USA
J Neurosci 24:2527-34. 2004..Neuron-specific proteolytic cleavage of apoE4 is associated with increased phosphorylation of tau and may play a key role in the development of AD-related neuronal deficits... - Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and neurodegenerationZhong Sheng Ji
Gladstone Institute of Neurological Disease, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA
J Biol Chem 281:2683-92. 2006..Thus, apoE4 and Abeta1-42 may work in concert in neurons to increase lysosome formation while increasing the susceptibility of lysosomal membranes to disruption, release of lysosomal enzymes into the cytosol, and neuronal degeneration... - Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's diseaseFaith M Harris
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 279:3862-8. 2004..Thus, neuronal expression of apoE is regulated by a diffusible factor or factors released from astrocytes, and this regulation depends on the activity of the Erk kinase pathway in neurons... - Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic targetShiming Ye
Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 102:18700-5. 2005..These findings provide insights into why apoE4 is associated with increased risk for Alzheimer's disease and may represent a potential target for drug development... - Intron-3 retention/splicing controls neuronal expression of apolipoprotein E in the CNSQin Xu
Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
J Neurosci 28:1452-9. 2008..Thus, neuronal expression of apoE is controlled by transcription of apoE-I3 under normal conditions and by processing of apoE-I3 into mature apoE mRNA in response to injury... - Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in miceYaisa Andrews-Zwilling
Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, California 94158, USA
J Neurosci 30:13707-17. 2010..Consequently, reducing Tau and enhancing GABA signaling are potential strategies to treat or prevent apoE4-related Alzheimer's disease... - Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic miceManuel Buttini
Gladstone Institute of Neurological Disease, San Francisco, CA 94158 2261, USA
Am J Pathol 177:563-9. 2010..Thus, an imbalance between astrocytic (excitoprotective) and neuronal (neurotoxic) apoE4 expression may increase susceptibility to diverse neurological diseases involving excitotoxic mechanisms... - GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin miceGang Li
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Cell Stem Cell 5:634-45. 2009..These findings suggest that GABAergic signaling can be targeted to mitigate the deleterious effects of apoE4 on neurogenesis... - Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicityShengjun Chang
Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 102:18694-9. 2005..Thus, the lipid- and receptor-binding regions in apoE4 fragments act together to cause mitochondrial dysfunction and neurotoxicity, which may be important in Alzheimer's disease pathogenesis... - Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neuronsHung Kai Chen
Gladstone Center for Translational Research, San Francisco, California 94158, USA
J Biol Chem 287:5253-66. 2012..Our results serve as a proof of concept that pharmacological intervention with apoE4 structure correctors negates apoE4 detrimental effects in neuronal cells and could be further developed as an Alzheimer disease therapeutic... - Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formationManuel Buttini
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141 9100, USA
J Neurosci 22:10539-48. 2002..Thus, apoE3, but not apoE4, delays age- and Abeta-dependent synaptic deficits through a plaque-independent mechanism. This difference could contribute to the differential effects of apoE isoforms on the risk and onset of AD... - Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locusQin Xu
Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
J Neurosci 26:4985-94. 2006..EGFPapoE reporter mice will be useful for studying the regulation of apoE expression in the CNS and might provide insights into the diverse mechanisms of apoE4-related neurodegeneration... - Hilar GABAergic interneuron activity controls spatial learning and memory retrievalYaisa Andrews-Zwilling
Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
PLoS ONE 7:e40555. 2012.... - Reducing human apolipoprotein E levels attenuates age-dependent Aβ accumulation in mutant human amyloid precursor protein transgenic miceNga Bien-Ly
Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
J Neurosci 32:4803-11. 2012..Moreover, Cre-mediated APOE4 gene excision in hippocampal astrocytes significantly reduced insoluble Aβ in adult mice. Thus, reducing, rather than increasing, apoE expression is an attractive approach to lowering brain Aβ levels... - Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer diseaseHung Kai Chen
Gladstone Center for Translational Research, San Francisco, California 94158, USA
J Biol Chem 286:5215-21. 2011..These results suggest that pharmacological intervention with small molecules that disrupt apoE4 domain interaction is a potential therapeutic approach for apoE4-carrying AD subjects... - Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctorsJens Brodbeck
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
J Biol Chem 286:17217-26. 2011..Correcting the pathological structure of apoE4 by disrupting domain interaction is a potential therapeutic approach to treat or prevent AD related to apoE4... - C-terminal-truncated apolipoprotein (apo) E4 inefficiently clears amyloid-beta (Abeta) and acts in concert with Abeta to elicit neuronal and behavioral deficits in miceNga Bien-Ly
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 108:4236-41. 2011..Thus, the C-terminal-truncated apoE4 fragment inefficiently clears Aβ peptides and acts in concert with low levels of Aβ to elicit neuronal and behavioral deficits in mice... - Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's diseaseRobert W Mahley
Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 103:5644-51. 2006.... - Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in TurksUgur Hodoglugil
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA, USA
J Lipid Res 47:144-53. 2006..At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California... - Evidence for differential effects of apoE3 and apoE4 on HDL metabolismPaul C R Hopkins
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141 9100, USA
J Lipid Res 43:1881-9. 2002.... - Apolipoprotein E4 domain interaction occurs in living neuronal cells as determined by fluorescence resonance energy transferQin Xu
Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94141, USA
J Biol Chem 279:25511-6. 2004..Thus, apoE4 domain interaction occurs in living neuronal cells and may be a molecular basis for apoE4-related neurodegeneration... - Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine developmentSachi Jain
Gladstone Institute of Neurological Disease, San Francisco, California, USA
PLoS ONE 7:e46340. 2012..Our findings suggest that Arf4 is a critical modulator of DG-mediated pattern separation by regulating dendritic spine development... - Apolipoprotein e sets the stage: response to injury triggers neuropathologyRobert W Mahley
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Neuron 76:871-85. 2012..Here, we review data supporting the hypothesis that apoE4 (> apoE3 > apoE2) has direct neurotoxic effects and highlight studies showing that blocking domain interaction reverses these detrimental effects... - Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathologyRobert W Mahley
Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, California 94158, United States
J Med Chem 55:8997-9008. 2012..Structure-corrector-based therapies could prove to be highly effective for the treatment of many protein-misfolding diseases... - Apolipoprotein E4 causes age- and sex-dependent impairments of hilar GABAergic interneurons and learning and memory deficits in miceLaura Leung
Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
PLoS ONE 7:e53569. 2012..These findings suggest that the sex-dependent effects of apoE4 on developing AD is in part attributable to inherent sex-based differences in the numbers of hilar GABAergic interneurons, which is further modulated by apoE genotype... - Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factorKaren L Ring
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Cell Stem Cell 11:100-9. 2012..Thus, self-renewable and multipotent iNSCs without tumorigenic potential can be generated directly from fibroblasts by reprogramming... - Putting cholesterol in its place: apoE and reverse cholesterol transportRobert W Mahley
Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
J Clin Invest 116:1226-9. 2006..In lower species, these large HDLs are not atherogenic. Thus, CETP might not be essential for reverse cholesterol transport in humans, raising hope of using a CETP inhibitor to elevate HDL levels... - Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cellsZhong Sheng Ji
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 277:21821-8. 2002.... - Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progressionTrevor D Burt
Division of Experimental Medicine, Department of Medicine, and Division of Neonatology, Department of Pediatrics, University of California, San Francisco, CA 94110, USA
Proc Natl Acad Sci U S A 105:8718-23. 2008.... - Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDSRobert W Mahley
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
J Lipid Res 50:S183-8. 2009..The next phase in our understanding of apoE will be characterized by clinical intervention to prevent or reverse the detrimental effects of apoE4 by modulating its structure or blocking the pathological processes it mediates... - Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neuronsJens Brodbeck
Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, The J David Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 105:1343-6. 2008..Rosiglitazone rescued this detrimental effect. Thus, rosiglitazone might improve cognition in AD patients by increasing dendritic spine density... - Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic miceFaith M Harris
Gladstone Institute of Neurological Disease, San Francisco, CA 94141 9100, USA
Proc Natl Acad Sci U S A 100:10966-71. 2003..Inhibiting their formation might inhibit apoE4-associated neuronal deficits... - Effect of domain interaction on apolipoprotein E levels in mouse brainGayathri Ramaswamy
Gladstone Institute of Neurological Disease, Departments of Pathology and Neurology, and Cardiovascular Research Institute, University of California, San Francisco, California 94158
J Neurosci 25:10658-63. 2005..Cells may recognize apoE4 and Arg-61 apoE as misfolded proteins and target them for degradation or accumulation. Thus, degradation/accumulation or lower levels of apoE4 may contribute to the association of apoE4 with Alzheimer's disease... - AAV serotype-1 mediates early onset of gene expression in mouse hearts and results in better therapeutic effectH Su
Cardiovascular Research Institute, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
Gene Ther 13:1495-502. 2006..Thus, AAV1 mediates earlier and higher transgene expression in myocardium and better therapeutic effects... - Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyondR W Mahley
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141 9100, USA
Curr Opin Lipidol 10:207-17. 1999..The isoform-specific effects of apolipoprotein E are currently being unraveled through detailed structure and function studies of this protein... - Apolipoprotein (apo) E4 and Alzheimer's disease: unique conformational and biophysical properties of apoE4 can modulate neuropathologyR W Mahley
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Acta Neurol Scand Suppl 185:8-14. 2006..It is predictable that apoE4 acts through various pathways to cause cognitive decline and neurodegeneration... - AAV serotype 1 mediates more efficient gene transfer to pig myocardium than AAV serotype 2 and plasmidH Su
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0793, USA
J Gene Med 10:33-41. 2008..AAV-mediated VEGF gene transfer can also induce neovascular formation in the pig myocardium... - Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine developmentSachi Jain
Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
PLoS ONE 8:e59478. 2013..These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4... - Detrimental effects of apolipoprotein E4: potential therapeutic targets in Alzheimer's diseaseRobert W Mahley
Gladstone Institute of Neurological Disease 1650 Owens Street, San Francisco, CA 94158, USA
Curr Alzheimer Res 4:537-40. 2007..Structural features that distinguish apoE4 and apoE3 determine their functional differences and hold the key to understanding how apoE4 is involved in Alzheimer's disease... - Atherogenic remnant lipoproteins: role for proteoglycans in trapping, transferring, and internalizingRobert W Mahley
Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
J Clin Invest 117:94-8. 2007.... - Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegenerationDaniel Zwilling
Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Cell 145:863-74. 2011..These findings support a critical link between tryptophan metabolism in the blood and neurodegeneration, and they provide a foundation for treatment of neurodegenerative diseases... - Common polymorphisms of ATP binding cassette transporter A1, including a functional promoter polymorphism, associated with plasma high density lipoprotein cholesterol levels in TurksUgur Hodoglugil
Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA
Atherosclerosis 183:199-212. 2005..In conclusion, we describe a functional promoter polymorphism (C-14T) and a coding sequence variant (V771M) of ABCA1 and their interactions with two other variants (R219K and I883M) on plasma HDL-C levels in Turks... - Age-related hippocampal changes in Bcl-2:Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with agingJ Savory
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
Neurotoxicology 20:805-17. 1999..These are novel observations which may have important implications for aiding in our understanding of the pathogenesis of neurodegeneration occurring in Alzheimer's disease... - ApoE and TDP-43 neuropathology in two siblings with familial FTLD-motor neuron diseaseKeith A Vossel
a Department of Neurology, University of California, San Francisco, CA, USA
Neurocase . 2012..Although differences seen in a sibling pair could arise due to chance, these findings raise the possibility that apoE4 exacerbates brain pathology in FTLD through formation of neurotoxic apoE fragments and interactions with TDP-43... - Alzheimer mechanisms and therapeutic strategiesYadong Huang
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Cell 148:1204-22. 2012..However, investigative and drug development efforts should be diversified to fully address the multifactoriality of the disease... - Electrostatic interactions of S4 voltage sensor in Shaker K+ channelD M Papazian
Department of Physiology, School of Medicine, University of California, Los Angeles 90024, USA
Neuron 14:1293-301. 1995..A simple structural hypothesis is proposed to account for the effects of the rescued double mutant combinations on the relative stabilities of open and closed channel conformations... - Apolipoprotein E2 transgenic rabbits. Modulation of the type III hyperlipoproteinemic phenotype by estrogen and occurrence of spontaneous atherosclerosisY Huang
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California 94141-9100, USA
J Biol Chem 272:22685-94. 1997..Therefore, high plasma levels of human apoE2 in transgenic rabbits result in a type III HLP phenotype, in which males have both more severe hyperlipidemia and more extensive atherosclerosis than females... - Gene expression in papillary thyroid carcinoma reveals highly consistent profilesY Huang
Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Pathology, Divisions of Sensory Biophysics and Endocrinology and Nuclear Medicine, Ohio State University, Columbus, OH 43210, USA
Proc Natl Acad Sci U S A 98:15044-9. 2001..We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use... - Overexpression and accumulation of apolipoprotein E as a cause of hypertriglyceridemiaY Huang
Gladstone Institute of Cardiovascular Disease, and Pathology, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 273:26388-93. 1998..The apoE3-overexpressing mice will be useful for studying the pathophysiology of this disorder... - Genetic factors precipitating type III hyperlipoproteinemia in hypolipidemic transgenic mice expressing human apolipoprotein E2Y Huang
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, USA
Arterioscler Thromb Vasc Biol 17:2817-24. 1997.... - Hypolipidemic and hyperlipidemic phenotypes in transgenic mice expressing human apolipoprotein E2Y Huang
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 271:29146-51. 1996..This animal model provides the opportunity to study the factors that cause hypolipidemia and those that precipitate the hyperlipidemia of type III HLP... - Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteinsY Huang
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141 9100, USA
J Biol Chem 273:17483-90. 1998..The increase in plasma cholesterol caused by apoE2 is due mostly to impaired clearance, whereas the increase in plasma triglycerides is caused mainly by apoE2-impaired lipolysis of triglyceride-rich lipoproteins... - ApoE genotype accounts for the vast majority of AD risk and AD pathologyJacob Raber
Departments of Behavioral Neuroscience and Neurology, L470, ONPRC, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97201, USA
Neurobiol Aging 25:641-50. 2004..Thus, the epidemiologic and basic science evidence suggest that apoE genotype accounts for the vast majority of AD risk and pathology...
Research Grants
- APOE EXPRESSION LEVEL MODULATES VLDL METABOLISMYadong Huang; Fiscal Year: 2003..abstract_text> ..