Research Topics
Species | ROBERT J VASSARSummaryAffiliation: Northwestern University Country: USA Publications
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Publications
The Alzheimer's ?-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulbTharinda W Rajapaksha
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Mol Neurodegener 6:88. 2011..Here, we used a genetic approach to investigate the function of BACE1 in axon guidance of olfactory sensory neurons (OSNs), a well-studied model of axon targeting in vivo...- The contribution of activated astrocytes to A? production: implications for Alzheimer's disease pathogenesisJie Zhao
Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
J Neuroinflammation 8:150. 2011..Here, we explored whether pro-inflammatory cytokines or A?42 would increase astrocytic levels of BACE1, APP, and ?-secretase processing, implying a feed-forward mechanism of astrocytic A? production... - The ?-secretase enzyme BACE1 as a therapeutic target for Alzheimer's diseaseRobert Vassar
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 300 E, Superior, Tarry 8 713, Chicago, IL 60611, USA
Alzheimers Res Ther 3:20. 2011..We conclude that therapeutic inhibition of BACE1 should be efficacious for AD, although careful titration of the drug dose may be necessary to limit mechanism-based side effects... - BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localizationBrian D Hitt
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Mol Neurodegener 5:31. 2010..Examination of BACE1-/- mice can provide insight into this function and also help anticipate consequences of BACE1 inhibition. Here we report a seizure-susceptibility phenotype that we have identified and characterized in BACE1-/- mice... - The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potentialRobert Vassar
Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA
J Neurosci 29:12787-94. 2009..The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE... - The Alzheimer's disease beta-secretase enzyme, BACE1Sarah L Cole
Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago Avenue, Chicago, IL, USA
Mol Neurodegener 2:22. 2007.... - Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's diseaseRobert Vassar
Department of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611 3006, USA
Neuron 54:671-3. 2007..In this issue of Neuron, Tesco et al. show that during apoptosis caspase-3 cleaves the adaptor protein GGA3, which is required for BACE lysosomal degradation, consequently stabilizing BACE and elevating Abeta generation... - The beta-secretase, BACE: a prime drug target for Alzheimer's diseaseR Vassar
Northwestern University Medical School, Department of Cell and Molecular Biology, Chicago, IL 60611, USA
J Mol Neurosci 17:157-70. 2001..In addition, I discuss recent studies of BACE1 knockout mice and the BACE1 X-ray structure, and relate implications for BACE1 drug development... - Beta-secretase (BACE) as a drug target for Alzheimer's diseaseRobert Vassar
Northwestern University Medical School, Department of Cell and Molecular Biology, 303 East Chicago Avenue, Chicago, IL 60611, USA
Adv Drug Deliv Rev 54:1589-602. 2002..Finally, recent studies of BACE1 knockout mice, the BACE1 X-ray structure, and implications for BACE1 drug development will be discussed... - BACE1: the beta-secretase enzyme in Alzheimer's diseaseRobert Vassar
The Feinberg School of Medicine, Northwestern University, Department of Cell and Molecular Biology, Chicago, IL 60611, USA
J Mol Neurosci 23:105-14. 2004..This review discusses the identification and initial characterization of BACE1 and BACE2, and summarizes recent studies of BACE1 knockout mice that have validated BACE1 as the authentic beta-secretase in vivo... - BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic miceMasuo Ohno
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 3008, USA
Neurobiol Dis 26:134-45. 2007..Our findings provide strong evidence that Abeta ultimately is responsible for neuron death in AD and validate the therapeutic potential of BACE1-inhibiting approaches for the treatment of AD... - Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesisTracy O'Connor
Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Neuron 60:988-1009. 2008..These results strongly suggest that eIF2alpha phosphorylation increases BACE1 levels and causes Abeta overproduction, which could be an early, initiating molecular mechanism in sporadic AD... - Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid raftsKulandaivelu S Vetrivel
Department of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 284:3793-803. 2009..These results indicate that post-translational S-palmitoylation of BACE1 is not required for APP processing, and that BACE1 can efficiently cleave APP in both raft and non-raft microdomains... - Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesisRodney A Velliquette
Department of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611, USA
J Neurosci 25:10874-83. 2005..This process may represent one of the earliest pathogenic events in AD... - Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesisJie Zhao
Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
J Neurosci 27:3639-49. 2007..We conclude that BACE1 elevation is most likely triggered by the amyloid pathway and may drive a positive-feedback loop in AD... - beta-Secretase, APP and Abeta in Alzheimer's diseaseRobert Vassar
Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Subcell Biochem 38:79-103. 2005..Here, I review the roles of BACE1, APP, and Abeta in AD and discuss the implications of therapeutic approaches that target BACE1 for the treatment of AD... - Beta-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer diseaseBrent L Kelly
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
J Biol Chem 280:31746-53. 2005..These data suggest a mechanism to explain the early cognitive loss without a major decline in synapse number observed in AD and propose a novel therapeutic target for AD intervention... - 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... - BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's diseaseMasuo Ohno
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Neuron 41:27-33. 2004..Our gene-based approach demonstrates that lower Abeta levels are beneficial for AD-associated memory impairments, validating BACE1 as a therapeutic target for AD... - Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formationHolly Oakley
Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
J Neurosci 26:10129-40. 2006..Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation... - Linking vascular disorders and Alzheimer's disease: potential involvement of BACE1Sarah L Cole
Northwestern University, The Feinberg School of Medicine, Department of Cell and Molecular Biology, 303 E Chicago Avenue, Chicago, IL 60611, USA
Neurobiol Aging 30:1535-44. 2009..However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation... - The role of amyloid precursor protein processing by BACE1, the beta-secretase, in Alzheimer disease pathophysiologySarah L Cole
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
J Biol Chem 283:29621-5. 2008..We address pertinent questions such as putative causes of BACE1 elevation in AD and discuss why, nine years since the identification of BACE1, treatments that address the underlying pathological mechanisms of AD are still lacking... - Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanismSarah L Cole
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
J Biol Chem 280:18755-70. 2005.... - BACE1 structure and function in health and Alzheimer's diseaseSarah L Cole
Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago Avenue, Chicago, IL, USA
Curr Alzheimer Res 5:100-20. 2008....
Research Grants
- BACE1 as a Therapeutic Target for Alzheimer's DiseaseROBERT J VASSAR; Fiscal Year: 2010..In addition, we will investigate the effects of BACE1 inhibition on the brain in order to understand potential side-effects of BACE1 inhibitor drugs. ..
- BACE1 as a Therapeutic Target for Alzheimer's DiseaseRobert Vassar; Fiscal Year: 2007..These Aims will test our overall hypothesis that BACE1 is a valid drug target, and we expect our results will strengthen the conceptual foundation for the development of BACE1 and gamma-secretase inhibitors for AD. ..
- Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's DiseaseRobert Vassar; Fiscal Year: 2007..Inhibition of BACE1 elevation should reduce A¿ without directly blocking BACE1 and thus may be efficacious without side-effects for Alzheimer's disease. ..
- Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's DiseaseROBERT J VASSAR; Fiscal Year: 2010..Inhibition of BACE1 elevation should reduce A without directly blocking BACE1 and thus may be efficacious without side-effects for Alzheimer's disease. ..