Research Topics
Genomes and Genes | William L KleinSummaryAffiliation: Northwestern University Country: USA Publications
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Publications
Amyloid beta oligomers induce impairment of neuronal insulin receptorsWei Qin Zhao
Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Dr, Hogan 5 110, Evanston, IL 60280, USA
FASEB J 22:246-60. 2008....- Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targetsWilliam L Klein
Department of Neurobiology and Physiology, Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Institute for Neuroscience, 2153 North Campus Drive, 60208, Evanston, IL, USA
Neurochem Int 41:345-52. 2002..The properties of ADDLs and their presence in AD-afflicted brain are consistent with their putative role even in the earliest stages of AD, including forms of mild cognitive impairment... 
Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomersFernanda G De Felice
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
Proc Natl Acad Sci U S A 106:1971-6. 2009..The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis...- Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}Wei Qin Zhao
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
J Biol Chem 284:18742-53. 2009..Our results suggest that dysfunctions of brain insulin and IGF-1 receptors contribute to Abeta aggregation and subsequent synaptic loss... - Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomersFernanda G De Felice
Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
Neurobiol Aging 29:1334-47. 2008..A beta oligomers have been increasingly implicated as the main neurotoxins in AD, and the current results provide a unifying mechanism in which oligomer activity is directly linked to tau hyperphosphorylation in AD pathology... - Targeting generation of antibodies specific to conformational epitopes of amyloid beta-derived neurotoxinsMary P Lambert
Northwestern University, Dept of Neurobiology and Physiology, and the Cognitive Neurology and Alzheimer s Disease Center, Evanston, IL 60208, USA
CNS Neurol Disord Drug Targets 8:65-81. 2009..It can be anticipated that further development of such antibodies for use in clinical trials will come in the near future... - Monoclonal antibodies that target pathological assemblies of AbetaMary P Lambert
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
J Neurochem 100:23-35. 2007.... - Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantineFernanda G De Felice
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
J Biol Chem 282:11590-601. 2007.... - Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's diseasePascale N Lacor
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
J Neurosci 27:796-807. 2007..The observed disruption of dendritic spines links ADDLs to a major facet of AD pathology, providing strong evidence that ADDLs in AD brain cause neuropil damage believed to underlie dementia... - Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensorAmanda J Haes
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA
J Am Chem Soc 127:2264-71. 2005.... - Alzheimer's-associated Abeta oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthalJason Pitt
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
Toxicol Appl Pharmacol 240:189-97. 2009..These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics... - Femtomole immunodetection of synthetic and endogenous amyloid-beta oligomers and its application to Alzheimer's disease drug candidate screeningLei Chang
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
J Mol Neurosci 20:305-13. 2003..The methods are suitable for screening combinatorial libraries and, importantly, provide the potential for simultaneous information on candidate transport across the blood-brain barrier... - Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's diseaseDimitra G Georganopoulou
Department of Chemistry and Institute of Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
Proc Natl Acad Sci U S A 102:2273-6. 2005..This study is a step toward a diagnostic tool, based on soluble pathogenic markers for the debilitating disease... - Aβ oligomer-induced synapse degeneration in Alzheimer's diseaseKyle C Wilcox
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
Cell Mol Neurobiol 31:939-48. 2011..We also discuss ways in which mechanistic insights from other diseases offer clues in the pursuit of the molecular basis of Alzheimer's disease... - Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1Masuo Ohno
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Eur J Neurosci 23:251-60. 2006..Our gene-based approach suggests that lowering soluble Abeta oligomers by inhibiting BACE1 may be beneficial for alleviating cognitive disorders in AD... - Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory lossYuesong Gong
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA
Proc Natl Acad Sci U S A 100:10417-22. 2003..Current results confirm the prediction that soluble oligomeric A beta ligands are intrinsic to AD pathology, and validate their use in new approaches to therapeutic AD drugs and vaccines... - Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrusHai-Wei Wang
Department of Pediatrics, Northwestern University Medical School and Evanston Hospital, Evanston, IL 60201, USA
Brain Res 924:133-40. 2002.... - Protection against the synaptic targeting and toxicity of Alzheimer's-associated Aβ oligomers by insulin mimetic chiro-inositolsJason Pitt
Department of Neurobiology, Northwestern University, Evanston, Illinois, USA
FASEB J 27:199-207. 2013..We propose that inositol glycans and DCI, a compound already established as safe for human consumption, have potential as AD therapeutics by protecting CNS synapses against Aβ oligomers through their insulin mimetic activity... - ADDLs & protofibrils--the missing links?William L Klein
Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Institute for Neuroscience, Evanston, IL 60208, USA
Neurobiol Aging 23:231-5. 2002 - Per-6-substituted beta-cyclodextrin libraries inhibit formation of beta-amyloid-peptide (A beta)-derived, soluble oligomersJiaxin Yu
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The University of Illinois at Chicago, 60612, USA
J Mol Neurosci 19:51-5. 2002..These preliminary experiments suggest that derivatized forms of beta-CD can interfere with the oligomerization process of A beta(1-42)... - Selective neuronal degeneration induced by soluble oligomeric amyloid beta proteinHyeon-Jin Kim
Research Division, Jinis Biopharmaceuticals Co, Chonju, Chonbuk, South Korea
FASEB J 17:118-20. 2003.... 
Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic modelChiho Hirata-Fukae
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA
Brain Res 1216:92-103. 2008..These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research...- Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer miceAnn C McKee
Department of Neurology, Boston University School of Medicine, Boston, MA, USA
Brain Res 1207:225-36. 2008..These findings provide further support for intraneuronal Abeta as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric Abeta accumulation... - Synaptic targeting by Alzheimer's-related amyloid beta oligomersPascale N Lacor
Neurobiology and Physiology Department, Northwestern University, Evanston, Illinois 60208, USA5
J Neurosci 24:10191-200. 2004..Results suggest the hypothesis that targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early AD... - Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathologySalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4545, USA
J Biol Chem 281:1599-604. 2006..Therefore, Abeta oligomers may play a role in the induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target... - PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42Olivier Boutaud
Department of Pharmacology, Vanderbilt University, Nashville 37232 6602, Tennessee, USA
J Neurochem 96:917-23. 2006.... - Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxictySiva Sundara Kumar Durairajan
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
Neurochem Int 52:741-50. 2008..These results suggest that Sal B has therapeutic potential in the treatment of AD, and warrant its study in animal models... - Per-6-substituted-per-6-deoxy beta-cyclodextrins inhibit the formation of beta-amyloid peptide derived soluble oligomersZhiqiang Wang
J Med Chem 47:3329-33. 2004..In the present work we describe the preparation of per-6-amino-6-deoxy-beta-cyclodextrins, which inhibit ADDLs formation in vitro... - Self-assembly of Abeta(1-42) into globular neurotoxinsBrett A Chromy
Biodefense Division, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, 7000 East Avenue, L-446, Livermore, California 94551, USA
Biochemistry 42:12749-60. 2003..The observed neurotoxicity, structure, and stability of synthetic Abeta(1-42) globular assemblies support the hypothesis that Abeta(1-42) oligomers play a role in triggering nerve cell dysfunction and death in Alzheimer's disease... - Cyclic AMP enhancers and Abeta oligomerization blockers as potential therapeutic agents in Alzheimer's diseaseFernanda G De Felice
Instituto de Bioquimica Medica, Programa de Bioquimica e Biofisica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944 590, Brazil
Curr Alzheimer Res 4:263-71. 2007..Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed... - Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegansYanjue Wu
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA
J Neurosci 26:13102-13. 2006....