Lennart Mucke

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β
    Elsa Suberbielle
    Gladstone Institute of Neurological Disease, San Francisco, California, USA
    Nat Neurosci 16:613-21. 2013
  2. pmc Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits
    Julie A Harris
    Gladstone Institute of Neurological Disease, San Francisco, CA, USA
    PLoS ONE 7:e45881. 2012
  3. pmc Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
    PLoS ONE 6:e29257. 2011
  4. pmc Neurotoxicity of amyloid β-protein: synaptic and network dysfunction
    Lennart Mucke
    Gladstone Institute of Neurological Disease and University of California, San Francisco, San Francisco, California, USA
    Cold Spring Harb Perspect Med 2:a006338. 2012
  5. ncbi request reprint High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California, San Francisco, California 94141 9100, USA
    J Neurosci 20:4050-8. 2000
  6. pmc Astroglial expression of human alpha(1)-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California San Francisco, San Francisco, California, USA
    Am J Pathol 157:2003-10. 2000
  7. ncbi request reprint Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model
    Erik D Roberson
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Science 316:750-4. 2007
  8. pmc Transsynaptic progression of amyloid-β-induced neuronal dysfunction within the entorhinal-hippocampal network
    Julie A Harris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 68:428-41. 2010
  9. pmc Neprilysin overexpression inhibits plaque formation but fails to reduce pathogenic Abeta oligomers and associated cognitive deficits in human amyloid precursor protein transgenic mice
    William J Meilandt
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 29:1977-86. 2009
  10. ncbi request reprint Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease
    Sarah Mueller-Steiner
    Gladstone Institute of Neurological Disease, University of California, San Francisco, 1650 Owens Street, 94158, USA
    Neuron 51:703-14. 2006

Detail Information

Publications60

  1. pmc Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β
    Elsa Suberbielle
    Gladstone Institute of Neurological Disease, San Francisco, California, USA
    Nat Neurosci 16:613-21. 2013
    ..Thus, transient increases in neuronal DSBs occur as a result of physiological brain activity, and Aβ exacerbates DNA damage, most likely by eliciting synaptic dysfunction...
  2. pmc Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits
    Julie A Harris
    Gladstone Institute of Neurological Disease, San Francisco, CA, USA
    PLoS ONE 7:e45881. 2012
    ..Thus, hTauP301L accumulation predominantly in the EC and related presynaptic pathology in hippocampal circuits was not sufficient to cause robust cognitive deficits within the age range analyzed here...
  3. pmc Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, California, United States of America
    PLoS ONE 6:e29257. 2011
    ..Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition...
  4. pmc Neurotoxicity of amyloid β-protein: synaptic and network dysfunction
    Lennart Mucke
    Gladstone Institute of Neurological Disease and University of California, San Francisco, San Francisco, California, USA
    Cold Spring Harb Perspect Med 2:a006338. 2012
    ..Modern analyses of this problem utilize electrophysiology coupled with synaptic biochemistry and behavioral phenotyping of animal models to elucidate the affected circuits and assess the effects of potential therapeutic interventions...
  5. ncbi request reprint High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California, San Francisco, California 94141 9100, USA
    J Neurosci 20:4050-8. 2000
    ..Our results support the emerging view that plaque-independent Abeta toxicity plays an important role in the development of synaptic deficits in AD and related conditions...
  6. pmc Astroglial expression of human alpha(1)-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California San Francisco, San Francisco, California, USA
    Am J Pathol 157:2003-10. 2000
    ..Our results demonstrate that hACT acts as an amyloidogenic co-factor in vivo and suggest that the role of hACT in AD is pathogenic...
  7. ncbi request reprint Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model
    Erik D Roberson
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Science 316:750-4. 2007
    ..Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions...
  8. pmc Transsynaptic progression of amyloid-β-induced neuronal dysfunction within the entorhinal-hippocampal network
    Julie A Harris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 68:428-41. 2010
    ..Thus, APP/Aβ expression in EC neurons causes transsynaptic deficits that could initiate the cortical-hippocampal network dysfunction in mouse models and human patients with AD...
  9. pmc Neprilysin overexpression inhibits plaque formation but fails to reduce pathogenic Abeta oligomers and associated cognitive deficits in human amyloid precursor protein transgenic mice
    William J Meilandt
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 29:1977-86. 2009
    ..Reduction of Abeta oligomers will likely be required for anti-Abeta treatments to improve cognitive functions...
  10. ncbi request reprint Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease
    Sarah Mueller-Steiner
    Gladstone Institute of Neurological Disease, University of California, San Francisco, 1650 Owens Street, 94158, USA
    Neuron 51:703-14. 2006
    ..Thus, CatB likely fulfills antiamyloidogenic and neuroprotective functions. Insufficient CatB activity might promote AD; increasing CatB activity could counteract the neuropathology of this disease...
  11. pmc Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease
    Erik D Roberson
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    J Neurosci 31:700-11. 2011
    ..Our results indicate that Aβ, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit...
  12. ncbi request reprint Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease
    Jorge J Palop
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 55:697-711. 2007
    ..Aberrant increases in network excitability and compensatory inhibitory mechanisms in the hippocampus may contribute to Abeta-induced neurological deficits in hAPP mice and, possibly, also in humans with AD...
  13. pmc Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease
    Rene O Sanchez-Mejia
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    Nat Neurosci 11:1311-8. 2008
    ..Inhibition of GIVA-PLA(2) may be beneficial in the treatment and prevention of Alzheimer's disease...
  14. ncbi request reprint Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice
    Walter 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...
  15. pmc Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease
    William J Meilandt
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    J Neurosci 28:5007-17. 2008
    ..We conclude that enkephalin elevations may contribute to cognitive impairments in hAPP mice and possibly in humans with AD. The therapeutic potential of reducing enkephalin production or signaling merits further exploration...
  16. pmc Collagen VI protects neurons against Abeta toxicity
    Jason S Cheng
    Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, California 94158, USA
    Nat Neurosci 12:119-21. 2009
    ..These results identify collagen VI as an important component of the neuronal injury response and demonstrate its neuroprotective potential...
  17. pmc Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model
    Pascal E Sanchez
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 109:E2895-903. 2012
    ..Our findings support the hypothesis that aberrant network activity contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might also help ameliorate related abnormalities in people who have or are at risk for AD...
  18. pmc Reversing EphB2 depletion rescues cognitive functions in Alzheimer model
    Moustapha Cisse
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    Nature 469:47-52. 2011
    ..Thus, depletion of EphB2 is critical in amyloid-β-induced neuronal dysfunction. Increasing EphB2 levels or function could be beneficial in Alzheimer's disease...
  19. ncbi request reprint Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease
    Jeannie Chin
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 25:9694-703. 2005
    ..Thus, increased Fyn expression is sufficient to trigger prominent neuronal deficits in the context of even relatively moderate Abeta levels, and inhibition of Fyn activity may help counteract Abeta-induced impairments...
  20. pmc Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor protein
    Julie 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...
  21. pmc Epilepsy and cognitive impairments in Alzheimer disease
    Jorge J Palop
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA
    Arch Neurol 66:435-40. 2009
    ..We conclude that beta-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis...
  22. ncbi request reprint High beta-secretase activity elicits neurodegeneration in transgenic mice despite reductions in amyloid-beta levels: implications for the treatment of Alzheimer disease
    Edward Rockenstein
    Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, California 92093 0624, USA
    J Biol Chem 280:32957-67. 2005
    ..Thus, inhibiting BACE1 may block not only Abeta-dependent but also Abeta-independent pathogenic mechanisms...
  23. pmc Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice
    Moustapha Cisse
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, San Francisco, California 94158, USA
    J Neurosci 31:10427-31. 2011
    ..Thus, at least in this model, PrP(c) is not an important mediator of Aβ-induced neurological impairments...
  24. ncbi request reprint Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease
    Jeannie Chin
    Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, California 94158, USA
    J Neurosci 27:2727-33. 2007
    ..We conclude that alterations in Reelin processing or signaling may be involved in AD-related neuronal dysfunction...
  25. pmc Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice
    Manuel 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...
  26. pmc Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease
    Binggui Sun
    Gladstone Institute of Neurological Disease, University of California, San Francisco, 94158, USA
    Cell Stem Cell 5:624-33. 2009
    ..Abeta-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD...
  27. ncbi request reprint Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice
    Jeannie Chin
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California 94141 9100, USA
    J Neurosci 24:4692-7. 2004
    ..We conclude that Fyn-dependent pathways are critical in AD-related synaptotoxicity and that the pathogenesis of hAPP/Abeta-induced neuronal alterations may be mechanistically heterogenous...
  28. ncbi request reprint Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice
    Luke Esposito
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 26:5167-79. 2006
    ..Whereas reductions in Sod2 would be expected to trigger or exacerbate neuronal and vascular pathology in AD, increasing Sod2 activity might be of therapeutic benefit...
  29. ncbi request reprint Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models
    Irene H Cheng
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    J Biol Chem 282:23818-28. 2007
    ..Thus, Abeta*56 is a likelier determinant of functional deficits in hAPP mice than fibrillar Abeta deposits. Therapeutic interventions that reduce Abeta fibrils at the cost of augmenting nonfibrillar Abeta assemblies could be harmful...
  30. pmc Selective targeting of microglia by quantum dots
    S Sakura Minami
    Gladstone Institute of Neurological Disease, 1650 Owens St, San Francisco, CA 94158, USA
    J Neuroinflammation 9:22. 2012
    ..Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases...
  31. pmc Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model
    Laure Verret
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Cell 149:708-21. 2012
    ..We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD...
  32. ncbi request reprint Altered navigational strategy use and visuospatial deficits in hAPP transgenic mice
    Amy R Deipolyi
    Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA
    Neurobiol Aging 29:253-66. 2008
    ..Interventions promoting flexibility in selecting learning strategies might help circumvent otherwise debilitating navigational deficits caused by AD-related hippocampal dysfunction...
  33. ncbi request reprint 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 formation
    Manuel 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...
  34. pmc Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neurobiol Aging 34:1523-9. 2013
    ..However, tau ablation did not cause significant dopaminergic impairments, and dopamine treatment did not improve the motor deficits, suggesting that they do not reflect extrapyramidal dysfunction...
  35. ncbi request reprint Vulnerability of dentate granule cells to disruption of arc expression in human amyloid precursor protein transgenic mice
    Jorge J Palop
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 25:9686-93. 2005
    ..The brain region-specific depletion of factors that participate in activity-dependent modification of synapses may critically contribute to cognitive deficits in hAPP mice and possibly in humans with Alzheimer's disease...
  36. pmc Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits
    Jorge J Palop
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94141, USA
    Proc Natl Acad Sci U S A 100:9572-7. 2003
    ....
  37. ncbi request reprint Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation
    Irene H Cheng
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    Nat Med 10:1190-2. 2004
    ..Amyloid plaques formed faster and were more extensive in Arctic mice than in hAPP mice expressing wild-type Abeta, even though Arctic mice had lower Abeta(1-42/1-40) ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo...
  38. pmc Tau reduction prevents Abeta-induced defects in axonal transport
    Keith A Vossel
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Science 330:198. 2010
    ..Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects...
  39. ncbi request reprint Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease
    Yadong 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...
  40. pmc Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: two faces of the same coin?
    Jorge J Palop
    Gladstone Institute of Neurological Disease and University of California, San Francisco, California, USA
    Neuromolecular Med 12:48-55. 2010
    ....
  41. ncbi request reprint Food for thought: essential fatty acid protects against neuronal deficits in transgenic mouse model of AD
    Lennart Mucke
    Gladstone Institute of Neurological Disease, University of California, San Francisco, PO Box 419100, 94103, USA
    Neuron 43:596-9. 2004
    ..report that a diet low in an essential omega-3 polyunsaturated fatty acid (docosahexaenoic acid) depletes postsynaptic proteins and exacerbates behavioral alterations in a transgenic mouse model of Alzheimer's disease...
  42. pmc Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice
    Faith 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...
  43. pmc Seizures and epileptiform activity in the early stages of Alzheimer disease
    Keith A Vossel
    Gladstone Institute of Neurological Disease, San Francisco, California2Memory and Aging Center, Department of Neurology, University of California, San Francisco, California
    JAMA Neurol 70:1158-66. 2013
    ..We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease...
  44. ncbi request reprint SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling
    Jennifer Chen
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Biol Chem 280:40364-74. 2005
    ..They also implicate SIRT1 in this pathway and highlight the therapeutic potential of resveratrol and other sirtuin-activating compounds in Alzheimer disease...
  45. doi request reprint Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: depletion of calcium-dependent proteins and inhibitory hippocampal remodeling
    Jorge J Palop
    Department of Neurology, Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA, USA
    Methods Mol Biol 670:245-62. 2011
    ..In addition, since we have found that the severity of these changes relates to the degree of Aβ-dependent cognitive impairments, the protocols are useful for quantifying biomarkers of cognitive impairment in mouse models of AD...
  46. pmc Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
    Jorge J Palop
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California, USA
    Nat Neurosci 13:812-8. 2010
    ..Strategies that block these Abeta effects may prevent cognitive decline in Alzheimer's disease. Potential obstacles and next steps toward this goal are discussed...
  47. ncbi request reprint A network dysfunction perspective on neurodegenerative diseases
    Jorge J Palop
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California 94158, USA
    Nature 443:768-73. 2006
    ..These ideas have far-reaching therapeutic implications...
  48. pmc Genes contributing to prion pathogenesis
    GULTEKIN TAMGUNEY
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA
    J Gen Virol 89:1777-88. 2008
    ....
  49. doi request reprint Paths of convergence: sirtuins in aging and neurodegeneration
    Li Gan
    Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA
    Neuron 58:10-4. 2008
    ..We will also examine the potential and challenges of targeting sirtuin pathways therapeutically...
  50. pmc The many faces of tau
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 70:410-26. 2011
    ..In this review, we highlight these functions and the potential roles of tau in neurodegenerative disease. We also discuss the therapeutic potential of drugs targeting various aspects of tau biology...
  51. ncbi request reprint Intracellularly generated amyloid-beta peptide counteracts the antiapoptotic function of its precursor protein and primes proapoptotic pathways for activation by other insults in neuroblastoma cells
    Luke Esposito
    Gladstone Institute of Neurological Disease, Department of Neurology, University of California, San Francisco, California, USA
    J Neurochem 91:1260-74. 2004
    ..We conclude that Abeta, especially intracellular Abeta, counteracts the antiapoptotic function of its precursor protein and predisposes cells to p53-mediated, and possibly other, proapoptotic pathways...
  52. ncbi request reprint Life extension factor klotho enhances cognition
    Dena B Dubal
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA Electronic address
    Cell Rep 7:1065-76. 2014
    ..Augmenting klotho or its effects may enhance cognition and counteract cognitive deficits at different life stages...
  53. pmc Alzheimer mechanisms and therapeutic strategies
    Yadong 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...
  54. pmc 100 years and counting: prospects for defeating Alzheimer's disease
    Erik D Roberson
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA
    Science 314:781-4. 2006
    ..The predicted increase in AD cases over the next few decades makes the development of better treatments a matter of utmost importance and urgency...
  55. ncbi request reprint Androgens protect against apolipoprotein E4-induced cognitive deficits
    Jacob Raber
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California 94141, USA
    J Neurosci 22:5204-9. 2002
    ..Our findings suggest that apoE4 contributes to cognitive decline by reducing AR levels in the brain, and that stimulating AR-dependent pathways can reverse apoE4-induced cognitive deficits...
  56. ncbi request reprint Inflammation in neurodegenerative disease--a double-edged sword
    Tony Wyss-Coray
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California San Francisco, San Francisco, CA 94141, USA
    Neuron 35:419-32. 2002
    ..Since many inflammatory responses are beneficial, directing and instructing the inflammatory machinery may be a better therapeutic objective than suppressing it...
  57. pmc RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice
    Ottavio Arancio
    Department of Psychiatry, Physiology and Neuroscience, Dementia Research Center, Nathan Kline Institute, New York University School of Medicine, NY 10032, USA
    EMBO J 23:4096-105. 2004
    ..These data indicate that RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction...
  58. pmc PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice
    Doo Sup Choi
    Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA
    Proc Natl Acad Sci U S A 103:8215-20. 2006
    ..These results indicate that increased neuronal PKCepsilon activity can promote Abeta clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity...
  59. ncbi request reprint Alzheimer's disease: A needle from the haystack
    Richard Morris
    Nature 440:284-5. 2006
  60. pmc Deficiency in neuronal TGF-beta signaling promotes neurodegeneration and Alzheimer's pathology
    Ina Tesseur
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
    J Clin Invest 116:3060-9. 2006
    ..These results show that reduced neuronal TGF-beta signaling increases age-dependent neurodegeneration and AD-like disease in vivo. Increasing neuronal TGF-beta signaling may thus reduce neurodegeneration and be beneficial in AD...

Research Grants25

  1. Role of APP and its Metabolites in Synaptic Degeneration
    Lennart Mucke; Fiscal Year: 2004
    ..It will also advance our understanding of the function of synaptic proteins in synapse loss and degeneration, which is the focus of RFA NS-01-002. ..
  2. Roles of Amyloid Precursor Protein and its Metabolites in Neuronal Impairment
    Lennart Mucke; Fiscal Year: 2010
    ..Ultimately, our study may provide useful guidance in the development of drugs to maintain and improve memory and other cognitive functions in AD. ..
  3. Roles of Amyloid Precursor Protein and its Metabolites in Neuronal Impairment
    Lennart Mucke; Fiscal Year: 2009
    ..Ultimately, our study may provide useful guidance in the development of drugs to maintain and improve memory and other cognitive functions in AD. ..
  4. Proteopathies of the Aging Central Nervous
    Lennart Mucke; Fiscal Year: 2007
    ..Our studies will shed light on diverse neurodegenerative diseases and could provide the knowledge needed to better treat and prevent them. ..
  5. Role of APP and its Metabolites in Synaptic Degeneration
    Lennart Mucke; Fiscal Year: 2006
    ..Ultimately, our study may provide useful guidance in the development of drugs to maintain and improve memory and other cognitive functions in AD. ..
  6. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2004
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  7. Role of APP and its Metabolites in Synaptic Degeneration
    Lennart Mucke; Fiscal Year: 2003
    ..It will also advance our understanding of the function of synaptic proteins in synapse loss and degeneration, which is the focus of RFA NS-01-002. ..
  8. Roles of Amyloid Precursor Protein and its Metabolites in Neuronal Impairment
    Lennart Mucke; Fiscal Year: 2009
    ..Ultimately, our study may provide useful guidance in the development of drugs to maintain and improve memory and other cognitive functions in AD. ..
  9. TRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASE
    Lennart Mucke; Fiscal Year: 2000
    ....
  10. TRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASE
    Lennart Mucke; Fiscal Year: 2000
    ....
  11. Roles of Amyloid Precursor Protein and its Metabolites in Neuronal Impairment
    Lennart Mucke; Fiscal Year: 2007
    ..Ultimately, our study may provide useful guidance in the development of drugs to maintain and improve memory and other cognitive functions in AD. ..
  12. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2005
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  13. TRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASE
    Lennart Mucke; Fiscal Year: 2001
    ....
  14. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2003
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  15. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2002
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  16. Role of APP and its Metabolites in Synaptic Degeneration
    Lennart Mucke; Fiscal Year: 2002
    ..It will also advance our understanding of the function of synaptic proteins in synapse loss and degeneration, which is the focus of RFA NS-01-002. ..
  17. Role of APP and its Metabolites in Synaptic Degeneration
    Lennart Mucke; Fiscal Year: 2001
    ..It will also advance our understanding of the function of synaptic proteins in synapse loss and degeneration, which is the focus of RFA NS-01-002. ..
  18. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2001
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  19. TRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASE
    Lennart Mucke; Fiscal Year: 1999
    ....