Nobuhisa Iwata

Summary

Affiliation: RIKEN Brain Science Institute
Country: Japan

Publications

  1. ncbi request reprint [Amyloid-beta peptide metabolism and Alzheimer's disease]
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Nihon Yakurigaku Zasshi 122:5-14. 2003
  2. ncbi request reprint Region-specific reduction of A beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan
    J Neurosci Res 70:493-500. 2002
  3. ncbi request reprint Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351 0198, Japan
    J Biol Chem 280:15229-37. 2005
  4. ncbi request reprint Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    J Neurosci 24:991-8. 2004
  5. ncbi request reprint Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation
    Takashi Saito
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Nat Med 11:434-9. 2005
  6. pmc Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Sci Rep 3:1472. 2013
  7. doi request reprint Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    FASEB J 26:1204-17. 2012
  8. ncbi request reprint Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function
    Shu Ming Huang
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 281:17941-51. 2006
  9. ncbi request reprint Single App knock-in mouse models of Alzheimer's disease
    Takashi Saito
    1 Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan 2 Japan Science and Technology Agency, Saitama, Japan
    Nat Neurosci 17:661-3. 2014
  10. ncbi request reprint Understanding molecular mechanisms of proteolysis in Alzheimer's disease: progress toward therapeutic interventions
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Biochim Biophys Acta 1751:60-7. 2005

Collaborators

Detail Information

Publications44

  1. ncbi request reprint [Amyloid-beta peptide metabolism and Alzheimer's disease]
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Nihon Yakurigaku Zasshi 122:5-14. 2003
    ..Since a number of receptors for neuropeptides are G-protein-coupled receptors, we would control brain Abetalevels pharmacologically by the manipulation of neprilysin activity...
  2. ncbi request reprint Region-specific reduction of A beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan
    J Neurosci Res 70:493-500. 2002
    ..These observations suggest that downregulation of neprilysin is likely to be related to AD pathology and to the A beta deposition associated with normal aging in humans...
  3. ncbi request reprint Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351 0198, Japan
    J Biol Chem 280:15229-37. 2005
    ....
  4. ncbi request reprint Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    J Neurosci 24:991-8. 2004
    ..Thus, presynaptic neprilysin has been demonstrated to degrade Abeta efficiently and to retard development of amyloid pathology...
  5. ncbi request reprint Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation
    Takashi Saito
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Nat Med 11:434-9. 2005
    ....
  6. pmc Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Sci Rep 3:1472. 2013
    ..AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary...
  7. doi request reprint Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    FASEB J 26:1204-17. 2012
    ..These findings implicate that calpain activation plays a pivotal role in the Aβ-triggered pathological cascade, highlighting a target for pharmacological intervention in the treatment of AD...
  8. ncbi request reprint Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function
    Shu Ming Huang
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 281:17941-51. 2006
    ..This supports the idea that a strategy to reduce Abeta oligomers in the brain by up-regulating neprilysin activity would contribute to alleviation of these symptoms...
  9. ncbi request reprint Single App knock-in mouse models of Alzheimer's disease
    Takashi Saito
    1 Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan 2 Japan Science and Technology Agency, Saitama, Japan
    Nat Neurosci 17:661-3. 2014
    ..The mice showed typical Aβ pathology, neuroinflammation and memory impairment in an age-dependent manner. ..
  10. ncbi request reprint Understanding molecular mechanisms of proteolysis in Alzheimer's disease: progress toward therapeutic interventions
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Biochim Biophys Acta 1751:60-7. 2005
    ....
  11. ncbi request reprint [Presymptomatic diagnosis, prevention and therapy]
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    No To Shinkei 57:855-66. 2005
  12. ncbi request reprint [Experimental gene therapy for Alzheimer's disease--animal models]
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute
    Nihon Rinsho 63:691-8. 2005
  13. doi request reprint Potent amyloidogenicity and pathogenicity of Aβ43
    Takashi Saito
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Nat Neurosci 14:1023-32. 2011
    ..These findings indicate that Aβ43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo...
  14. ncbi request reprint Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology
    Shinjiro Fukami
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Neurosci Res 43:39-56. 2002
    ....
  15. ncbi request reprint Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice
    Jiro Takano
    Laboratories for Proteolytic Neuroscience and Behavioral Genetics, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 280:16175-84. 2005
    ..These mutant mice will serve as useful tools for investigating calpain involvement in various diseases...
  16. ncbi request reprint Alzheimer's disease, neuropeptides, neuropeptidase, and amyloid-beta peptide metabolism
    Takashi Saito
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Sci Aging Knowledge Environ 2003:PE1. 2003
    ....
  17. ncbi request reprint Effects of neprilysin chimeric proteins targeted to subcellular compartments on amyloid beta peptide clearance in primary neurons
    Emi Hama
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 279:30259-64. 2004
    ....
  18. ncbi request reprint 19F and 1H MRI detection of amyloid beta plaques in vivo
    Makoto Higuchi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitoma 351 0198, Japan
    Nat Neurosci 8:527-33. 2005
    ..This approach could be used in longitudinal studies in mouse models of Alzheimer disease to search for biomarkers associated with amyloid beta pathology as well as to track disease course after treatment with candidate medications...
  19. doi request reprint Aβ secretion and plaque formation depend on autophagy
    Per Nilsson
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan Electronic address
    Cell Rep 5:61-9. 2013
    ..Our results establish a function for autophagy in Aβ metabolism: autophagy influences secretion of Aβ to the extracellular space and thereby directly affects Aβ plaque formation, a pathological hallmark of AD. ..
  20. doi request reprint Gene therapy in Alzheimer's disease - potential for disease modification
    Per Nilsson
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    J Cell Mol Med 14:741-57. 2010
    ..Overall, the prospects appear hopeful that gene therapy has the potential to be a disease modifying treatment for AD...
  21. ncbi request reprint Metabolism of amyloid-beta peptide and Alzheimer's disease
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    Pharmacol Ther 108:129-48. 2005
    ..Thus, it may be possible to pharmacologically control brain Abeta levels with somatostatin receptor agonists...
  22. pmc Comprehensive behavioral phenotyping of calpastatin-knockout mice
    Ryuichi Nakajima
    RIKEN Brain Science Institute, Saitama, Japan
    Mol Brain 1:7. 2008
    ..However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive behavioral test battery...
  23. ncbi request reprint Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease. Towards presymptomatic diagnosis, prevention and therapy
    Takaomi C Saido
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Neurosci Res 54:235-53. 2006
    ..We also introduce a novel non-invasive amyloid imaging approach using a high-power magnetic resonance imaging (MRI) for the presymptomatic diagnosis of AD...
  24. ncbi request reprint [Identification of the major A beta 1-42-degrading catabolic pathway in brain parenchyma]
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198
    Seikagaku 75:97-107. 2003
  25. doi request reprint Efficient four-drug cocktail therapy targeting amyloid-β peptide for Alzheimer's disease
    Masashi Asai
    Department of Pharmacology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
    J Neurosci Res 88:3588-97. 2010
    ..Moreover, the four-drug cocktail treatment caused no changes in processing of the γ-secretase substrate Notch. This is suggests that this cocktail treatment could be a new therapeutic approach for AD...
  26. ncbi request reprint In vivo role of caspases in excitotoxic neuronal death: generation and analysis of transgenic mice expressing baculoviral caspase inhibitor, p35, in postnatal neurons
    Masanori Tomioka
    Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Brain Res Mol Brain Res 108:18-32. 2002
    ..These results indicate that p35-inhibitable caspases play rather minor roles in the kainate-induced excitotoxicity and that the relative contribution of calpain is likely to be greater than that of caspases...
  27. ncbi request reprint In vivo glioma growth requires host-derived matrix metalloproteinase 2 for maintenance of angioarchitecture
    Megumi Takahashi
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Pharmacol Res 46:155-63. 2002
    ..These observations suggest that glioma induces MMP-2 and utilizes its activity in the host tissue to support angiogenesis and to maintain angioarchitecture...
  28. ncbi request reprint Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography
    Jun Maeda
    Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba 263 8555, Japan
    J Neurosci 27:10957-68. 2007
    ....
  29. ncbi request reprint Oxidized neprilysin in aging and Alzheimer's disease brains
    Deng Shun Wang
    Department of Neuroscience and Pathology Neuropathology, Mayo Clinic, Jacksonville, FL 32224, USA
    Biochem Biophys Res Commun 310:236-41. 2003
    ..These findings suggest that decreased NEP may contribute to Abeta deposition in AD and that age-related oxidative damage to NEP may play a role in age-related cerebral amyloidosis that is exacerbated in AD...
  30. ncbi request reprint [Therapeutic strategy by manipulating some protease activities for Alzheimer's disease]
    Nobuhisa Iwata
    Nihon Yakurigaku Zasshi 131:320-5. 2008
  31. ncbi request reprint Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease
    Masahiro Maruyama
    Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
    Ann Neurol 57:832-42. 2005
    ....
  32. ncbi request reprint Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory
    Li Bo Zou
    Department of Pharmacology, School of Pharmacy, Shenyang Pharmaceutical University, China
    J Pharmacol Exp Ther 317:334-40. 2006
    ....
  33. ncbi request reprint Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid beta and impairment of learning and memory
    Akihiro Mouri
    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma cho, Showa Ku, Nagoya 466 8560, Japan
    Behav Brain Res 168:83-91. 2006
    ....
  34. ncbi request reprint Fluoro-substituted and 13C-labeled styrylbenzene derivatives for detecting brain amyloid plaques
    Kumi Sato
    Dojindo Laboratories, Tabaru 2025 5, Mashiki machi, Kumamoto 861 2202, Japan
    Eur J Med Chem 39:573-8. 2004
    ..Because of the possession of a nuclide with a quantized angular momentum, both FSB and [(13)C]BSB are also potential contrast agents for magnetic resonance imaging to locate AD pathologies in vivo...
  35. ncbi request reprint Part of membrane-bound Abeta exists in rafts within senile plaques in Tg2576 mouse brain
    Hideko Kokubo
    Gunma University School of Health Sciences, 3 39 15 Showa Machi, 371 8514 Maebashi, Japan
    Neurobiol Aging 26:409-18. 2005
    ..This study ultrastructurally demonstrated that part of membrane-bound Abeta exists in lipid rafts within senile plaques, and suggests that rafts could be one of the sites for initial Abeta deposition...
  36. ncbi request reprint Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen
    Jiying Wang
    Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
    J Immunol 181:712-20. 2008
    ..These findings link four factors that have been suggested to be associated with AMD: inflammation, complement activation, Abeta deposition, and drusen...
  37. ncbi request reprint Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model
    Chiho 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...
  38. ncbi request reprint Oligomeric proteins ultrastructurally localize to cell processes, especially to axon terminals with higher density, but not to lipid rafts in Tg2576 mouse brain
    Hideko Kokubo
    Gunma University School of Health Sciences, 3 39 15 Showa Machi, Maebashi 371 8514, Japan
    Brain Res 1045:224-8. 2005
    ..The oligomer was less frequently colocalized to flotillin-1-immunoreactive rafts than Abeta42, suggesting that rafts are one of the sites of polymeric Abeta deposition, but not of oligomeric proteins including Abeta...
  39. pmc Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta
    Kulandaivelu S Vetrivel
    Department of Neurobiology and Neurology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 283:19489-98. 2008
    ..In view of the known function of CD147 in MMP production, we postulate that CD147 expression influences Abeta levels by an indirect mechanism involving MMPs that can degrade extracellular Abeta...
  40. ncbi request reprint Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model
    Yasumasa Yoshiyama
    The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Neuron 53:337-51. 2007
    ..Thus, hippocampal synaptic pathology and microgliosis may be the earliest manifestations of neurodegenerative tauopathies, and abrogation of tau-induced microglial activation could retard progression of these disorders...
  41. ncbi request reprint Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease Abeta secretion
    Masashi Asai
    Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro Hongo, Iruma gun, Saitama 350 0495, Japan
    Biochem Biophys Res Commun 352:498-502. 2007
    ..Our results indicate that berberine would be a promising candidate for the treatment of AD...
  42. pmc The potential role of amyloid beta in the pathogenesis of age-related macular degeneration
    Takeshi Yoshida
    Department of Ophthalmology and Visual Science and Instrumental Analysis Research Center, Tokyo Medical and Dental University, Tokyo, Japan
    J Clin Invest 115:2793-800. 2005
    ..Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD...
  43. ncbi request reprint Altered expression of neprilysin family members in the pituitary gland of sleep-disturbed rats, an animal model of severe fatigue
    Tokiko Ogawa
    Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, Asahimachi, Osaka, Japan
    J Neurochem 95:1156-66. 2005
    ..These results suggest that peptide processing and degradation in the pituitary may be an influential factor in fatigued states such as sleep disturbance...
  44. ncbi request reprint The novel beta-secretase inhibitor KMI-429 reduces amyloid beta peptide production in amyloid precursor protein transgenic and wild-type mice
    Masashi Asai
    Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan
    J Neurochem 96:533-40. 2006
    ..Our results indicate that the beta-secretase inhibitor KMI-429 is a promising candidate for the treatment of AD...