Research Topics
| F M LaFerlaSummaryAffiliation: University of California Country: USA Publications
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Publications
Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer's disease miceGrace E Stutzmann
Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4550, USA
J Neurosci 26:5180-9. 2006..We conclude that lifelong ER Ca2+ disruptions in AD are related to a modulation of RyR signaling associated with PS1 mutations and represent a discrete "calciumopathy," not merely an acceleration of normal aging...- Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's diseaseVeerendra Kumar Madala Halagappa
Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA
Neurobiol Dis 26:212-20. 2007..We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies... 
Pathways linking Abeta and tau pathologiesFrank M LaFerla
Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA
Biochem Soc Trans 38:993-5. 2010....- An array of genes implicated in Alzheimer's diseaseFrank M LaFerla
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697 4545, USA
Neurobiol Aging 27:1078-80. 2006..In addition, the utilization of transgenic mouse models will no doubt also be of tremendous value for gene expression studies as they permit investigations at well-defined stages of pathology and cognitive function... - Intracellular amyloid-beta in Alzheimer's diseaseFrank M LaFerla
Department of Neurobiology and Behaviour, and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4545, USA
Nat Rev Neurosci 8:499-509. 2007.... - Calcium dyshomeostasis and intracellular signalling in Alzheimer's diseaseFrank M LaFerla
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, California 92697, USA
Nat Rev Neurosci 3:862-72. 2002 - Regional hypomyelination and dysplasia in transgenic mice with astrocyte-directed expression of interferon-gammaF M LaFerla
Department of Neurobiology and Behavior, University of California, Irvine 92697 4545, USA
J Mol Neurosci 15:45-59. 2000.... - Subcellular mechanisms of presenilin-mediated enhancement of calcium signalingM A Leissring
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California at Irvine, 1109 Gillespie Neuroscience Research Facility, Irvine, California 92697-4545, USA
Neurobiol Dis 8:469-78. 2001.... - Presenilin-2 mutations modulate amplitude and kinetics of inositol 1, 4,5-trisphosphate-mediated calcium signalsM A Leissring
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4545, USA
J Biol Chem 274:32535-8. 1999..The finding that mutations in both PS1 and PS2 modulate intracellular calcium signaling suggests that these disturbances may represent a common pathogenic mechanism of presenilin-associated FAD... - Blocking Abeta42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein: a mechanistic link between Abeta and tau pathologySalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
J Neurosci 28:12163-75. 2008..These data highlight the critical role CHIP plays as a link between Abeta and tau and identify CHIP as a new potential target not only for AD but for other neurodegenerative disorders characterized by tau accumulation... - Enhanced caffeine-induced Ca2+ release in the 3xTg-AD mouse model of Alzheimer's diseaseIan F Smith
Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4545, USA
J Neurochem 94:1711-8. 2005.... - M1 receptors play a central role in modulating AD-like pathology in transgenic miceAntonella Caccamo
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
Neuron 49:671-82. 2006..Therefore, selective M1 agonists may be efficacious for the treatment of AD... 
A dynamic relationship between intracellular and extracellular pools of AbetaSalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Bldg, Irvine, CA 92697 4545, USA
Am J Pathol 168:184-94. 2006..Taken together, these results provide strong experimental evidence that intraneuronal Abeta may serve as a source for some of the extracellular amyloid deposits...- Injury induces presenilin-1 gene expression in mouse brainD H Cribbs
Department of Neurology, University of California, Irvine 92697 4550, USA
Neuroreport 7:1773-6. 1996..These findings underscore the epidemiological evidence that implicate head injury as a risk factor for AD and suggest a possible role for PS-1 in this capacity... - Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotauKim N Green
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697 4545, USA
J Neurosci 28:11500-10. 2008..These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability... - Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic miceSalvatore Oddo
Department of Neurobiology and Behavior, Institute for Brain Aging and Dementia, University of California, Irvine, California, USA
J Neurochem 102:1053-63. 2007.... - Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's diseaseKim N Green
Department of Neurobiology and Behavior, and Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697 4545, USA
J Neurosci 26:9047-56. 2006..These findings suggest that high levels of glucocorticoids, found in AD, are not merely a consequence of the disease process but rather play a central role in the development and progression of AD... - Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's diseaseSalvatore Oddo
Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4545, USA
Neurobiol Aging 24:1063-70. 2003.... - Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's diseaseSalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 102:3046-51. 2005..Finally, this study highlights the importance of testing compounds designed to ameliorate AD pathology in a model with both neuropathological lesions because of the differential effects it can have on either Abeta or tau... - Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin miceM A Leissring
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory and Institute for Brain Aging and Dementia, University of California Irvine 92697 4561, USA
J Cell Biol 149:793-8. 2000..Collectively, our findings suggest that the overfilling of calcium stores represents the fundamental cellular defect underlying the alterations in calcium signaling conferred by presenilin mutations... - Amyloid-beta expression in retrosplenial cortex of triple transgenic mice: relationship to cholinergic axonal afferents from medial septumR T Robertson
Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA
Neuroscience 164:1334-46. 2009..These results suggest that the septal cholinergic axonal projections transport Abeta or amyloid precursor protein (APP) to layer III of RSg... - Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer diseaseMathew Blurton-Jones
Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 106:13594-9. 2009..Taken together, our findings demonstrate that neural stem cells can ameliorate complex behavioral deficits associated with widespread Alzheimer disease pathology via BDNF... - Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tanglesAntonella Caccamo
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Bldg, Irvine, CA 92697 4545, USA
Am J Pathol 170:1669-75. 2007..These results, however, suggest that the most efficacious treatment will be combining lithium with other anti-A beta interventions... - Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunctionSalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
Neuron 39:409-21. 2003.... - Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasomeSalvatore Oddo
Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA 92697, USA
Neuron 43:321-32. 2004..These findings indicate that Abeta immunization may be useful for clearing both hallmark lesions of AD, provided that intervention occurs early in the disease course... - 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... - Role of calcium in the pathogenesis of Alzheimer's disease and transgenic modelsK N Green
Department of Neurobiology and Behavior, University of California, Irvine CA 92697 4545, USA
Subcell Biochem 45:507-21. 2007.... - Genetically altering Abeta distribution from the brain to the vasculature ameliorates tau pathologySalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697 4545, USA
Brain Pathol 19:421-30. 2009..The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Abeta deposits... - Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's diseaseMasashi Kitazawa
Department of Neurobiology and Behavior, University of California Irvine, California 92697 4545, USA
J Neurosci 25:8843-53. 2005..Therefore, this study clearly demonstrates that microglial activation exacerbates key neuropathological features such as tangle formation... - Genetically augmenting Abeta42 levels in skeletal muscle exacerbates inclusion body myositis-like pathology and motor deficits in transgenic miceMasashi Kitazawa
Department of Neurobiology and Behavior, 1109 Gillespie Neuroscience Facility, University of California, Irvine, Irvine, CA 92697 4545, USA
Am J Pathol 168:1986-97. 2006..The data presented here provide experimental evidence that Abeta42 plays a proximal and critical role in the muscle degenerative process... - Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tanglesSalvatore Oddo
Departments of Neurobiology and Behavior and Neurology, and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697, USA
J Biol Chem 281:39413-23. 2006..Notably, reducing soluble Abeta alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Abeta immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice... - Long term changes in phospho-APP and tau aggregation in the 3xTg-AD mice following cerebral ischemiaM A Koike
Department of Neurobiology and Behavior, University of California, Irvine, CA, United States
Neurosci Lett 495:55-9. 2011..Furthermore, we found an increase in insoluble total tau 3-months post-injury. Together these findings further elucidate the long-term impact of cerebral hypoperfusion on Alzheimer's disease... - Abeta inhibits the proteasome and enhances amyloid and tau accumulationBertrand P Tseng
Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4545, USA
Neurobiol Aging 29:1607-18. 2008..These findings provide further evidence that the proteasome represents a viable target for therapeutic intervention in AD... - Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD miceLani K Clinton
Department of Neurobiology and Behavior, 1109 Gillespie Neuroscience Research Facility, University of California, Irvine, Irvine, CA 92697 4545, USA
Neurobiol Dis 28:76-82. 2007..Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks... - Immunization with amyloid-beta attenuates inclusion body myositis-like myopathology and motor impairment in a transgenic mouse modelMasashi Kitazawa
Department of Neurobiology and Behavior and Neurology, University of California, Irvine, California 92697 4545, USA
J Neurosci 29:6132-41. 2009..These findings provide support for the hypothesis that Abeta is one of the key pathogenic components in IBM pathology and subsequent skeletal muscle degeneration... - Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of ADMasashi Kitazawa
Department of Neurobiology and Behavior, University of California, Irvine, California, USA
J Neurochem 108:1550-60. 2009..Taken together, our data suggest that chronic copper exposure accelerates not only amyloid pathology but also tau pathology in a mouse model of AD... - Learning decreases A beta*56 and tau pathology and ameliorates behavioral decline in 3xTg-AD miceLauren M Billings
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697 4545, USA
J Neurosci 27:751-61. 2007..These findings indicate that, in young and middle-aged 3xTg-AD mice, repeated spatial training can significantly delay the development of neuropathology and decline in spatial memory... - Pathways by which Abeta facilitates tau pathologyMathew Blurton-Jones
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4545, USA
Curr Alzheimer Res 3:437-48. 2006..We propose that the four putative mechanisms described in this review likely mediate the interactions between Abeta and tau, thereby leading to the development of AD neurodegeneration... - Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylationAnna Parachikova
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697 4545, USA
J Alzheimers Dis 21:527-42. 2010.... - Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathologyRobert A Rissman
Institute for Brain Aging and Dementia, University of California, Irvine 92697, USA
J Clin Invest 114:121-30. 2004..These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline... - Ca2+ signaling in mouse cortical neurons studied by two-photon imaging and photoreleased inositol triphosphateGrace E Stutzmann
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697 4550, USA
J Neurosci 23:758-65. 2003..Metabotropic signaling via the phosphoinositide pathway thus serves as a powerful and sustained modulator of excitability in cortical neurons and displays complex reciprocal interactions between electrical and chemical signals... - Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive declineLani K Clinton
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697 4545, USA
J Neurosci 30:7281-9. 2010..Together, our data support the notion that Abeta, tau, and alpha-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction... - Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disordersAntonella Caccamo
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Bldg, Irvine, CA 92697-4545, USA
Neurobiol Aging 26:645-54. 2005..These findings suggest that age- and region-specific changes in the proteolytic clearance of Abeta represent a critical pathogenic mechanism that may account for the susceptibility of particular brain or muscle regions in AD and IBM... - Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic miceLauren M Billings
Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA
Neuron 45:675-88. 2005..Reemergence of the Abeta pathology again leads to cognitive deficits. This study strongly implicates intraneuronal Abeta in the onset of cognitive dysfunction... - Alzheimer's disease: Abeta, tau and synaptic dysfunctionFrank M LaFerla
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4545, USA
Trends Mol Med 11:170-6. 2005.... - Oligemic hypoperfusion differentially affects tau and amyloid-{beta}Maya A Koike
Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 3212 Biological Sciences III, Irvine, CA 92697 4545, USA
Am J Pathol 177:300-10. 2010..This finding may have implications for the pathogenesis of AD, as it indicates for the first time that total tau and amyloid-beta are differentially impacted by mild hypoperfusion... - Memantine improves cognition and reduces Alzheimer's-like neuropathology in transgenic miceHilda Martinez-Coria
Department of Neurobiology and Behavior, University of California, Irvine, 3400A Biological Sciences III, Irvine, CA 92697 4545, USA
Am J Pathol 176:870-80. 2010..These results suggest that the effects of memantine treatment on AD brain include disease modification and prevention of synaptic dysfunction... - Linking calcium to Abeta and Alzheimer's diseaseKim N Green
Department of Neurobiology and Behavior and Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA 92697 4545, USA
Neuron 59:190-4. 2008..Finally, new studies have elucidated the role by which presenilins modulate calcium signaling, including effects on SERCA2b and gating of the IP(3) receptor, and lead to Abeta production... - Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitabilityGrace E Stutzmann
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697 4550, USA
J Neurosci 24:508-13. 2004..Even in young animals, PS1 mutations have profound effects on neuronal Ca2+ and electrical signaling: cumulatively, these disruptions may contribute to the long-term pathophysiology of AD... - Widespread neuronal expression of the presenilin-1 early-onset Alzheimer's disease gene in the murine brainD H Cribbs
Department of Neurology, University of California, Irvine, USA
Am J Pathol 148:1797-806. 1996..Overall, it appears that the pattern of presenilin-1 gene expression parallels that previously described for the amyloid precursor protein... - Multiphoton-evoked color change of DsRed as an optical highlighter for cellular and subcellular labelingJ S Marchant
Laboratory of Cellular and Molecular Neurobiology, University of California, Irvine, CA 92697-4550, USA
Nat Biotechnol 19:645-9. 2001..We describe optimal parameters to induce the color change of DsRed, and demonstrate applications that show the potential of this optical highlighter... - Calsenilin reverses presenilin-mediated enhancement of calcium signalingM A Leissring
Laboratories of Molecular Neuropathogenesis, and Molecular and Cellular Neurobiology, Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4545, USA
Proc Natl Acad Sci U S A 97:8590-3. 2000.... - SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta productionKim N Green
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA
J Cell Biol 181:1107-16. 2008..Our results point to a physiological role for the presenilins in Ca(2+) signaling via regulation of the SERCA pump... - Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseMaria I Fonseca
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
J Immunol 183:1375-83. 2009..e., C5aR) can interfere with neuroinflammation and neurodegeneration in AD rodent models, suggesting a novel therapeutic target for reducing pathology and improving cognitive function in human AD patients... - Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscleMichael C Sugarman
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 99:6334-9. 2002..These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM... - Neural stem cells improve memory in an inducible mouse model of neuronal lossTritia R Yamasaki
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
J Neurosci 27:11925-33. 2007..These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss... - Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levelsKim N Green
Department of Neurobiology and Behavior, University of California, Irvine, California 92697 4545, USA
J Neurosci 27:4385-95. 2007..Collectively, these results suggest that DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD... - A physiologic signaling role for the gamma -secretase-derived intracellular fragment of APPMalcolm A Leissring
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 99:4697-702. 2002.... - Calcium dysregulation in Alzheimer's disease: recent advances gained from genetically modified animalsIan F Smith
Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Building, Irvine CA 92697-4545, USA
Cell Calcium 38:427-37. 2005..The cause of synaptic dysfunction is unknown but it is likely that amyloid-beta and its ability to disrupt intracellular calcium homeostasis plays a key role in this process... - Relevance of transgenic mouse models to human Alzheimer diseaseDebbi A Morrissette
Department of Neurobiology and Behavior and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4545, USA
J Biol Chem 284:6033-7. 2009..This review discusses the utility of transgenic mice as a research tool and their contributions to our understanding of Alzheimer disease... - The role of nicotinic acetylcholine receptors in Alzheimer's diseaseSalvatore Oddo
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545, USA
J Physiol Paris 99:172-9. 2006..In this review, we consider the role of nicotinic acetylcholine receptors in transgenic models and in AD... - Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic modelMichael C Sugarman
Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Facility, Irvine, CA 92697 4545, USA
Neurobiol Aging 27:423-32. 2006..These findings also highlight parallels between the MCK-betaAPP mice and the human IBM condition... - Microglia as a potential bridge between the amyloid beta-peptide and tauMasashi Kitazawa
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, 92697-4545, USA
Ann N Y Acad Sci 1035:85-103. 2004..In this review, we discuss the molecular mechanism of inflammatory responses in AD brain as well as animal models, and current therapies using NSAIDs, antioxidants, and immunotherapy as neuroprotective strategies for AD... - Presenilin regulates capacitative calcium entry dependently and independently of gamma-secretase activityYama Akbari
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4545, USA
Biochem Biophys Res Commun 322:1145-52. 2004..These data suggest that changes in the structural components of presenilin can modulate CCE independent of its function in gamma-secretase activity and intracellular calcium stores... - Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase-3betaMasashi Kitazawa
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697 4545, USA
Ann Neurol 64:15-24. 2008..Here, we address the mechanisms by which inflammation modulates Abeta and tau, two hallmark features of this disease... - Amyloid beta-peptide: the inside storyBertrand P Tseng
Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4545, USA
Curr Alzheimer Res 1:231-9. 2004..Here we review recent evidence supporting a pathogenic role for intracellular Abeta in AD, Down syndrome, and IBM... - Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxiaVikram G Shakkottai
Department of Physiology and Biophysics, University of California Irvine, 92697, USA
J Clin Invest 113:582-90. 2004..This dominant-inhibitory strategy may help define the in vivo role of SK channels in other neuronal pathways... - IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosomeLeslie Michels Thompson
Department of Psychiatry and Human Behavior, University of California, Irvine, 92697, USA
J Cell Biol 187:1083-99. 2009..Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species... - Antipodal effects of p25 on synaptic plasticity, learning, and memory--too much of a good thing is badFrank M LaFerla
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Research Facility, Irvine, California 92697, USA
Neuron 48:711-2. 2005..This work demonstrates the complexity of Cdk5/p25 in neuronal function and shows that dysregulation of a factor involved in plasticity can cause neurodegeneration... - M1 agonists as a potential disease-modifying therapy for Alzheimer's diseaseAntonella Caccamo
Department of Neurobiology, University of California, Irvine, Irvine, CA 92697, USA
Curr Alzheimer Res 6:112-7. 2009..In this review, we discuss the role of M1 agonists as a potential disease-modifying therapy for Alzheimer's disease... - Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's diseaseEmily R Rosario
Neuroscience Graduate Program, University of Southern California, Los Angeles, California 90089, USA
J Neurosci 26:13384-9. 2006..In addition, our finding that DHT protects against acceleration of AD-like neuropathology predicts that androgen-based hormone therapy may be a useful strategy for the prevention and treatment of AD in aging men... - Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer's disease at early pathological stageYasuji Matsuoka
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA
J Mol Neurosci 31:165-70. 2007..Our results indicate that NAP treatment of transgenic mice initiated at an early stage reduced both Abeta and tau pathology, suggesting that NAP might be a potential therapeutic agent for AD... - Congo red and thioflavin-T analogs detect Abeta oligomersIzumi Maezawa
M I N D Institute and Department of Pathology, University of California Davis, Sacramento, California 95817, USA
J Neurochem 104:457-68. 2008..We propose that by improving the binding affinity of current ligands, in vivo imaging of AbetaO is feasible by a 'signal subtraction' procedure. This approach may facilitate the identification of individuals with early AD... - Deglycosylated anti-amyloid beta antibodies reduce microglial phagocytosis and cytokine production while retaining the capacity to induce amyloid beta sequestrationKazuyuki Takata
Department of Neurobiology, Kyoto Pharmaceutical University and 21st Century COE Program, Kyoto 607 8414, Japan
Eur J Neurosci 26:2458-68. 2007..We conclude that deglycosylated antibodies effectively induced Abeta sequestration without provoking neuroinflammation; thus, these deglycosylated antibodies may be optimal for sequestration therapy for Alzheimer's disease... - 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... - Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD miceJenna C Carroll
Neuroscience Graduate Program, Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA
J Neurosci 27:13357-65. 2007..These results demonstrate that estrogen and progesterone independently and interactively regulate AD-like neuropathology and suggest that an optimized hormone therapy may be useful in reducing the risk of AD in postmenopausal women... - Increased intraneuronal resting [Ca2+] in adult Alzheimer's disease miceJose R Lopez
Department of Anesthesia, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Neurochem 105:262-71. 2008..These results demonstrate that an elevation in resting [Ca2+](i), contributed by aberrant Ca2+entry and release pathways, should be considered a major component of the abnormal Ca2+ homeostasis associated with AD...
Research Grants
- Modulating IBM pathology in transgenic miceFrank LaFerla; Fiscal Year: 2005....
- Regulation of calcium signaling pathways by presenilinsFrank LaFerla; Fiscal Year: 2005..Lastly, by manipulating calcium signaling and determining its effects on AB production, aim 5 will address whether the effects of presenilin mutations on calcium signaling are necessary and/or sufficient to increase Ab formation. ..
- Gene interactions in a model of Alzheimer's diseaseFrank LaFerla; Fiscal Year: 2007..In aim 3, we will determine if calcium dyshomeostasis underlies the synaptic dysfunction and propose to develop a novel transgenic mouse the expresses a calcium indicator protein (inverse pericam) in neurons. ..
- Learning and Memory Impairments in a Transgenic AD Model with Plaques and TanglesFrank LaFerla; Fiscal Year: 2007....
- Gene interactions in a model of Alzheimer's diseaseFrank LaFerla; Fiscal Year: 2009..This proposal seeks to determine the impact that co-morbidities such as ischemia and stress play on the development of AD in the 3xTg-AD mouse model. ..
- Learning and Memory Impairments in a Transgenic AD Model with Plaques and TanglesFrank M LaFerla; Fiscal Year: 2010....
- Gene Interactions in a Model of Alzheimer's DiseaseFrank M LaFerla; Fiscal Year: 2010..This proposal seeks to determine the impact that co-morbidities such as ischemia and stress play on the development of AD in the 3xTg-AD mouse model. ..