Research Topics
Genomes and GenesSpecies | Dale BredesenSummaryAffiliation: Buck Institute for Age Research Country: USA Publications
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Publications
Receptors that mediate cellular dependenceD E Bredesen
The Buck Institute for Age Research, Novato, CA 94945, USA
Cell Death Differ 12:1031-43. 2005..Cellular dependence receptors, considered in the aggregate, may thus form a system of molecular integration, analogous to the electrical integration system provided by dendritic arbors in the nervous system...
Valosin-containing protein gene mutations: cellular phenotypes relevant to neurodegenerationKaren S Poksay
The Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
J Mol Neurosci 44:91-102. 2011....
Improved prediction of critical residues for protein function based on network and phylogenetic analysesBoris Thibert
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
BMC Bioinformatics 6:213. 2005....- Apoptosis: overview and signal transduction pathwaysD E Bredesen
Buck Institute for Age Research, Novato, California, USA
J Neurotrauma 17:801-10. 2000..Activated caspases are the executioners of the apoptotic program, and carry out this function by cleaving specific cellular substrates. Modulation of this process holds promise as a therapeutic approach in neurotrauma... - Toward a mechanistic taxonomy of cell death programsDale E Bredesen
Buck Institute and UCSF, USA
J Alzheimers Dis 6:S3-6. 2004 - Key note lecture: toward a mechanistic taxonomy for cell death programsDale E Bredesen
Buck Institute for Age Research, CA 94945, USA
Stroke 38:652-60. 2007..Both anti-pcd and pro-pcd modulators play prominent roles in development and disease, including ischemic cerebrovascular disease. The purpose of this article is therefore to review the basics of programmed cell death... - Apoptosis and dependence receptors: a molecular basis for cellular addictionDale E Bredesen
The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
Physiol Rev 84:411-30. 2004..Thus these receptors may serve in caspase amplification, and in so doing create cellular states of dependence on their respective ligands... - Cell death in the nervous systemDale E Bredesen
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA
Nature 443:796-802. 2006..Surprisingly, although the cell death itself may occur relatively late in the course of the degenerative process, the mediators of the underlying cell-death pathways have shown promise as potential therapeutic targets... - The non-existent aging program: how does it work?Dale E Bredesen
Buck Institute for Age Research, University of California, San Francisco, 8001 Redwood Blvd, Novato, CA 94949, USA
Aging Cell 3:255-9. 2004.... - Rebuttal to Austad: 'Is aging programmed?Dale E Bredesen
Buck Institute for Age Research, University of California, San Francisco, 8001 Redwood Blvd, Novato, CA 94949, USA
Aging Cell 3:261-2. 2004 - Programmed cell death mechanisms in neurological diseaseDale E Bredesen
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, California 94945, USA
Curr Mol Med 8:173-86. 2008.... - Neurodegeneration in Alzheimer's disease: caspases and synaptic element interdependenceDale E Bredesen
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA USA 94945
Mol Neurodegener 4:27. 2009..Here we review the effects and implications of this cleavage event, and propose a model of Alzheimer's disease that focuses on the critical nature of this cleavage and its downstream effects... - APP-based neuroprotective strategiesDale E Bredesen
Buck Institute for Age Research and University of California, San Francisco, USA
Curr Alzheimer Res 4:541-3. 2007..Here we discuss the possibility that APP-mediated signal transduction, downstream from amyloid-beta peptide production itself, may be an appropriate therapeutic target in Alzheimer's disease... 
Importance of the caspase cleavage site in amyloid-β protein precursorDale E Bredesen
Buck Institute for Age Research, Novato, CA 94945, USA
J Alzheimers Dis 22:57-63. 2010..Here we review the results and implications of these studies for the understanding of Alzheimer's disease pathophysiology and the potential development of therapeutics that target this site in AβPP...- Selective vulnerability in Alzheimer's disease: amyloid precursor protein and p75(NTR) interactionJoanna Fombonne
The Buck Institute for Age Research, Novato, CA 94945, USA
Ann Neurol 65:294-303. 2009..However, the relation between amyloid precursor protein (APP) and p75(NTR) has not been described previously... - Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathwayRammohan V Rao
Buck Institute for Age Research, Novato, California 94945 and the Department of Medicine III, Johannes Gutenberg University, Mainz D 55101, Germany
J Biol Chem 277:21836-42. 2002..Thus, ER stress-induced programmed cell death defines a novel, mitochondrial and Apaf-1-independent, intrinsic apoptotic pathway... - Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664Veronica Galvan
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
Proc Natl Acad Sci U S A 103:7130-5. 2006..These results suggest that Asp-664 plays a critical role in the generation of Alzheimer-related pathophysiological and behavioral changes in human APP transgenic mice, possibly as a cleavage site or via protein-protein interactions... - Novel mediators of amyloid precursor protein signalingAndrzej Swistowski
Buck Institute for Age Research, Novato, California 94945, USA
J Neurosci 29:15703-12. 2009..These results define new mediators of the signal transduction network mediated by APP... - Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78Rammohan V Rao
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945 1400, USA
FEBS Lett 514:122-8. 2002..These results define a novel protective role for GRP78 in preventing ER stress-induced cell death... - Coupling endoplasmic reticulum stress to the cell death program in dopaminergic cells: effect of paraquatShankar J Chinta
The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
Neuromolecular Med 10:333-42. 2008..Our results indicate a protective role for p23 in PD-related programmed cell death. The data also underscore the involvement of ER, caspases, and the proteasomal system in ER stress-induced cell death process... - Caspase cleavage of members of the amyloid precursor family of proteinsVeronica Galvan
Buck Institute for Age Research, Novato, California 94945-1400, USA
J Neurochem 82:283-94. 2002..Our results suggest that even though APLP1 and APLP2 cannot generate Abeta, they may potentially contribute to the pathology of AD by generating peptide fragments whose toxicity is comparable to that of APPC31... - Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor proteinJulie A Harris
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, San Francisco, California 94158, USA
J Neurosci 30:372-81. 2010..Thus, caspase cleavage of APP at position D664 and generation of C31 do not play a critical role in the development of these abnormalities... - Target-assisted iterative screening reveals novel interactors for PSD95, Nedd4, Src, Abl and Crk proteinsAlexei Kurakin
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
J Biomol Struct Dyn 19:1015-29. 2002..The novel screening format, dubbed TAIS (target-assisted iterative screening), is discussed as an alternative platform to existing technologies for a pair-wise characterization of protein-protein interactions... - An unconventional IAP-binding motif revealed by target-assisted iterative screening (TAIS) of the BIR3-cIAP1 domainAlexei Kurakin
The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
J Mol Recognit 20:39-50. 2007..A 'two-pocket' model of BIR domain recognition mechanism is proposed as the basis of differential BIR domain interactions with different IBMs... - An artificially designed pore-forming protein with anti-tumor effectsH Michael Ellerby
Program on Cancer and Aging, The Buck Institute, Novato, California 94945, USA
J Biol Chem 278:35311-6. 2003..We propose and validate a mechanism for the selectivity of SGP toward cell membranes in tumors. SGP is the prototype for a new class of artificial proteins designed for therapeutic applications... - Interaction of ASK1 and the beta-amyloid precursor protein in a stress-signaling complexVeronica Galvan
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
Neurobiol Dis 28:65-75. 2007..Thus, ASK1 may be the apical MAPKKK in a signaling complex assembled with APP as a response to stress... - Long-term prevention of Alzheimer's disease-like behavioral deficits in PDAPP mice carrying a mutation in Asp664Veronica Galvan
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
Behav Brain Res 191:246-55. 2008..Our results thus further demonstrate that the D664A mutation either completely precludes, or markedly delays (beyond 13 mo) the appearance of AD-like deficits in this mouse model of AD... - C-terminal cleavage of the amyloid-beta protein precursor at Asp664: a switch associated with Alzheimer's diseaseSurita Banwait
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
J Alzheimers Dis 13:1-16. 2008.... - Alternative, nonapoptotic programmed cell death: mediation by arrestin 2, ERK2, and Nur77Susana Castro-Obregon
Buck Institute for Age Research, Novato, California 94945 1400, USA
J Biol Chem 279:17543-53. 2004..These results suggest that Nur77, which is regulated by a MAPK pathway activated via arrestin 2, modulates NK(1)R-mediated nonapoptotic pcd... - Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screeningAlexei V Kurakin
Buck Institute for Age Research, Novato, California 94945, USA
J Biol Chem 278:34102-9. 2003..A direct interaction of synaptojanin 1 and PAK2 with CIN85 SH3 domains was confirmed by Far Western blotting... - Ten years on: mediation of cell death by the common neurotrophin receptor p75(NTR)Shahrooz Rabizadeh
The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945 1400, USA
Cytokine Growth Factor Rev 14:225-39. 2003..Results to date suggest that these functions are mediated through different underlying mechanisms, and that their respective signaling pathways are cell type and co-receptor dependent... - Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic miceAlyson L Peel
Buck Institute for Age Research, Novato, CA, USA
Neurobiol Dis 14:52-62. 2003..These findings support a role for PKR activation in the pathogenesis of AD... - Misfolded proteins, endoplasmic reticulum stress and neurodegenerationRammohan V Rao
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945 1400, USA
Curr Opin Cell Biol 16:653-62. 2004..Dissecting these pathways should be valuable in understanding the pathogenesis of, and ultimately in designing therapy for, neurodegenerative diseases that feature misfolded proteins... - Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's diseasePatricia Spilman
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
PLoS ONE 5:e9979. 2010..Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined... - The PDZ domain as a complex adaptive systemAlexei Kurakin
The Buck Institute for Age Research, Novato, California, USA
PLoS ONE 2:e953. 2007..The generalization of this reconceptualization in regard to other protein interaction modules and specific protein associations is consistent with the image of the cell as a complex adaptive macromolecular system as opposed to clockwork... - Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulationJessica E Young
Buck Institute for Age Research, Novato, California, 94945, USA
J Biol Chem 282:30150-60. 2007..Our results, thus, suggest that proteolytic processing of ataxin-7 by caspase-7 may contribute to SCA7 disease pathogenesis... - Endoplasmic reticulum stress-induced cell death in dopaminergic cells: effect of resveratrolShankar J Chinta
The Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
J Mol Neurosci 39:157-68. 2009.... - Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicityDaniel C Lu
Department of Neurosciences, University of California, San Diego, La Jolla 92093, USA
J Neurochem 87:733-41. 2003..These findings link C31 generation and its potential cell death activity to Abeta cytotoxicity, the leading mechanism proposed for neuronal death in AD... - Signal transduction in Alzheimer disease: p21-activated kinase signaling requires C-terminal cleavage of APP at Asp664Thuy Vi V Nguyen
Buck Institute for Age Research, Novato, California 94945, USA
J Neurochem 104:1065-80. 2008..These findings are compatible with previous suggestions that PAK may be involved in the pathophysiology of AD, and demonstrate that both early activation and late inactivation in the murine AD model require the cleavage of APP at Asp664... - Mechanism of cytotoxicity mediated by the C31 fragment of the amyloid precursor proteinSun Ah Park
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
Biochem Biophys Res Commun 388:450-5. 2009.... - Reversal of learning deficits in hAPP transgenic mice carrying a mutation at Asp664: a role for early experienceJunli Zhang
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, United States
Behav Brain Res 206:202-7. 2010..Our results suggest that early experience reduces the contribution of non-cognitive components of behaviour to performance, and may contribute to the restoration of learning at later ages in PDAPP(D664A) mice... - Differential regulation of the intrinsic pathway of apoptosis in brain and liver during ageingVeronika Stoka
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
FEBS Lett 580:3739-45. 2006..These results suggest that a decrease in apoptosis activation during ageing is not tissue-specific, but rather displays a complex dependence on species and strains of animals... - Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) miceKunlin Jin
Buck Institute for Age Research, Novato, CA 94945, USA
Proc Natl Acad Sci U S A 101:13363-7. 2004..Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential... - PLAIDD, a type II death domain protein that interacts with p75 neurotrophin receptorHarald Frankowski
Buck Institute for Age Research, Novato, CA 94945 1400, USA
Neuromolecular Med 1:153-70. 2002..Both isoforms of PLAIDD could be co-immunoprecipitated with p75NTR, suggesting an interaction between these molecules... - A pilot proteomic study of amyloid precursor interactors in Alzheimer's diseaseBarbara A Cottrell
Buck Institute for Age Research, Novato, CA 94945, USA
Ann Neurol 58:277-89. 2005..In agreement with previous studies, our results are compatible with an involvement of APP in axonal transport and vesicular trafficking, and with a potential association of APP with cellular protein folding/protein degradation systems... - Tau phosphorylation in Alzheimer's disease: potential involvement of an APP-MAP kinase complexAlyson L Peel
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
Neuromolecular Med 5:205-18. 2004..2003), these results suggest a model of AD in which Abeta peptide dimerizes APP directly, leading to the activation of ASK1, MKK6, and p38, with subsequent phosphorylation of tau at sites characteristic of AD... - Neurogenesis in the adult brain: implications for Alzheimer's diseaseVeronica Galvan
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
CNS Neurol Disord Drug Targets 6:303-10. 2007.... - Target-assisted iterative screening of phage surface display cDNA librariesAlexei Kurakin
Buck Institute for Age Research, Novato, CA, USA
Methods Mol Biol 264:47-60. 2004..The described application is a method of choice for the researchers interested in the identification and characterization of novel protein-protein interactions mediated by peptide recognition domains... - Developmental shift in the apostat: comparison of neurones and astrocytesVeronika Stoka
Buck Institute for Age Research, Novato, CA 94945, USA
FEBS Lett 579:6147-50. 2005.... - Science fact and the SENS agenda. What can we reasonably expect from ageing research?Huber Warner
Buck Institute for Age Research, Novato, CA, USA
EMBO Rep 6:1006-8. 2005 - Molecular components of a cell death pathway activated by endoplasmic reticulum stressRammohan V Rao
The Buck Institute for Age Research, Novato, California 94945, USA
J Biol Chem 279:177-87. 2004..Our data identify two molecules, valosin-containing protein and apoptosis-linked gene-2 (ALG-2), that appear to play a role in mediating ER stress-induced cell death... - Differential regulation of Smac/DIABLO and Hsp-70 during brain maturationVeronika Stoka
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
Neuromolecular Med 9:255-63. 2007..These results indicate that the activation pattern of the intrinsic pathway of apoptosis undergoes a marked shift during postnatal maturation... - Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1)Veronica Galvan
Buck Institute for Age Research, Novato, California 94945 1400, USA
J Biol Chem 278:13325-32. 2003.... - A novel motif identified in dependence receptorsGabriel Del Rio
Buck Institute for Age Research, Novato, California, United States of America
PLoS ONE 2:e463. 2007..To date, we have not identified a function for this putative domain. We speculate that the DART motif may be involved in protein processing, interaction with other proteins or lipids, or homomultimerization... - Efficient identification of critical residues based only on protein structure by network analysisMichael P Cusack
Buck Institute for Age Research, Novato, California, United States of America
PLoS ONE 2:e421. 2007..A unique feature of the method is the inclusion of the conformational diversity of proteins in the prediction, thus reproducing a basic feature of the structure/function relationship of proteins... - Deficits in synaptic transmission and learning in amyloid precursor protein (APP) transgenic mice require C-terminal cleavage of APPMichael J Saganich
Salk Institute for Biological Studies, La Jolla, California 92037, USA
J Neurosci 26:13428-36. 2006..These results indicate that cleavage of APP may play a critical role in the development of synaptic and behavioral dysfunction in APP transgenic mice... - Hunter-killer peptide (HKP) for targeted therapyH Michael Ellerby
College of Pharmacy, Touro University, Mare Island, Vallejo, California 94592, USA
J Med Chem 51:5887-92. 2008 - Coupling endoplasmic reticulum stress to the cell death program in mouse melanoma cells: effect of curcuminJason Bakhshi
Terra Linda High School, 320 Nova Albion Way, San Rafael, CA 94903, USA
Apoptosis 13:904-14. 2008..Our studies demonstrate that curcumin triggers ER stress and the activation of specific cell death pathways that feature caspase cleavage and activation, p23 cleavage, and downregulation of the anti-apoptotic Mcl-1 protein... - Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexesDaniel C Lu
Department of Neurosciences, University of California-San Diego, 9500 Gilman Drive, Mail Code 0691, La Jolla, CA 92093-0691, USA
Ann Neurol 54:781-9. 2003.... - Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-beta peptides via p75NTR/PLAIDDYuichi Hashimoto
Department of Pharmacology, Keio University School of Medicine, Shinanomachi, Tokyo, Japan
J Neurochem 90:549-58. 2004..In addition, we found that HN, ADNF, IGF-I, or bFGF inhibits both pathways of Abeta-induced neurotoxicity mediated by p75NTR... - Netrin-1 controls colorectal tumorigenesis by regulating apoptosisLaetitia Mazelin
Apoptosis Differentiation Laboratory Equipe labellisée La Ligue Molecular and Cellular Genetic Center, CNRS UMR 5534, University of Lyon, 69622 Villeurbanne, France
Nature 431:80-4. 2004..These data demonstrate that netrin-1 can promote intestinal tumour development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumour suppressors... - Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. 1985Robert M Levy
J Neurosurg 107:1253-73; discussion 1251. 2007 - siRNA-based inhibition specific for mutant SOD1 with single nucleotide alternation in familial ALS, compared with ribozyme and DNA enzymeTakanori Yokota
Department of Neurology, Tokyo Medical and Dental University, Tokyo, Japan
Biochem Biophys Res Commun 314:283-91. 2004..Our results support the feasibility of utilizing siRNA-based gene therapy of familial ALS with mutant SOD1... - Meeting report: cellular dependence--old concept, new mechanismsPatrick Mehlen
Centre Genetique Moleculaire et Cellulaire, , CNRS UMR5534, University of Lyon, Lyon, France
Sci STKE 2003:pe55. 2003..With several of the receptors implicated in various human developmental disorders or disease states, gaining an understanding of the molecular mechanisms controlling dependence receptor-mediated cell death has clear clinical relevance... - Targeting the prostate for destruction through a vascular addressWadih Arap
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 99:1527-31. 2002..These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk...
Research Grants
- MECHANISM OF INHIBITION OF NEURODEGENERATION AND AGINGDale Bredesen; Fiscal Year: 1999..The potential findings have important implications for the process of aging and degenerative disease. ..
- Buck Institute--Pharmacology of Lifespan ExtensionDale Bredesen; Fiscal Year: 2005..Drs. Dale Bredesen, Simon Melov, Gordon Lithgow and David Greenberg will organize the scientific program...
- Training in Age-Related Disease and Aging ResearchDale Bredesen; Fiscal Year: 2006..abstract_text> ..
- Mechanism of apoptosis induction by the receptor DCCDale Bredesen; Fiscal Year: 2007..abstract_text> ..
- Development and Improvement of an Animal Resource CoreDale Bredesen; Fiscal Year: 2007....
- Novel apoptotic pathway activated by misfolded proteinsDale Bredesen; Fiscal Year: 2007..abstract_text> ..
- Basic Mechanisms in Aging and Age Related DiseaseDale Bredesen; Fiscal Year: 2007....
- Novel Prionic Mechanism Underlying Alzheimer?s DiseaseDale Bredesen; Fiscal Year: 2009..We have provided evidence that the prevailing view of Alzheimer's disease is incorrect, and have developed a new model that offers insight into the mechanism and potential treatment of this important and common disease. ..
- MECHANISM OF INHIBITION OF NEURODEGENERATION AND AGINGDale Bredesen; Fiscal Year: 2005....
- Center for Integrative Studies of AgingDale Bredesen; Fiscal Year: 2004....
- Novel Prionic Mechanism Underlying Alzheimer?s DiseaseDale E Bredesen; Fiscal Year: 2010..We have provided evidence that the prevailing view of Alzheimer's disease is incorrect, and have developed a new model that offers insight into the mechanism and potential treatment of this important and common disease. ..