A5016024085- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Evolutionary Game Theory and Cooperation
- Cellular transport and secretion
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Parkinson's Disease Mechanisms and Treatments
- Microtubule and mitosis dynamics
- Evolutionary Psychology and Human Behavior
- Linguistic Variation and Morphology
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Protein Structure and Dynamics
- Dementia and Cognitive Impairment Research
- Drug Transport and Resistance Mechanisms
- Language and cultural evolution
- Genetic Neurodegenerative Diseases
- Animal Behavior and Reproduction
- Nuclear Receptors and Signaling
- Wnt/β-catenin signaling in development and cancer
- Computational Drug Discovery Methods
- S100 Proteins and Annexins
- Neurological diseases and metabolism
- Primate Behavior and Ecology
- Mitochondrial Function and Pathology
- Trace Elements in Health
The University of Tokyo
2012-2024
Google (United States)
2009-2023
Doshisha University
2012-2021
Japan Science and Technology Agency
1997-2020
Advanced Algorithm and Systems (Japan)
2013-2014
Japan Synchrotron Radiation Research Institute
2013-2014
University of California, San Francisco
2013
New Energy and Industrial Technology Development Organization
2012
Hanalei Watershed Hui
2006
Tokyo University of the Arts
2006
A neuropathological hallmark of Alzheimer disease (AD) is a widespread amyloid deposition. We analyzed the entire amino acid sequences in an preparation and found, addition to major beta/A4-protein (A beta) fragment, two unknown peptides. raised antibodies against synthetic peptides using subsequences these These immunostained neuritic diffuse plaques as well vascular amyloid. Electron microscopic analysis demonstrated that immunostaining was localized on fibrils. have isolated apparently...
Paired helical filaments (PHF), which constitute a distinct type of pathological neuronal fiber, are the principal constituent neurofibrillary tangles that occur in brain patients with Alzheimer's disease. Their insolubility sodium dodecyl sulfate and urea has prevented analysis their subunit composition by gel electrophoresis. A monoclonal antibody (DF2) was isolated specifically labeled PHF at both light electron microscopic levels. It small polypeptide (5 kilodaltons) shown to be...
To gain insight into the abnormal phosphorylation of PHF-tau, we have determined sites by identifying phosphopeptides means ion spray mass spectrometry followed sequencing ethanethiol-modified peptides. Nineteen been identified; all but Ser-262 are localized to amino- and carboxyl-terminal flanking regions microtubule-binding domain. Eleven correspond fetal type sites. Unexpectedly, 10 non-proline-directed, whereas others proline-directed. Thus, PHF-tau can be considered consist additional...
Antisera to paired helical filaments (PHF) were found contain a significant amount of tau antibodies specific for phosphorylated form, but only negligible those non-phosphorylated form. Also, the tau-specific antibodies, not ones, labeled neurofibrillary tangles isolated in presence sodium dodecyl sulfate (SDS) and stained both senile plaque neurites fixed tissue sections very similar way as whole antiserum did. Taken together, these results strongly suggest that major antigenic determinant...
Amyloid β protein (Aβ), a pathogenic molecule associated with Alzheimer's disease, is produced by γ-secretase, which cleaves the β-carboxyl terminal fragment (βCTF) of β-amyloid precursor in middle its transmembrane domain. How cleavage proceeds within membrane has long been enigmatic. We hypothesized previously that βCTF cleaved first at membrane–cytoplasm boundary, producing two Aβs, Aβ 48 and 49 , are processed further releasing three residues each step to produce 42 40 respectively. To...
Tau with unusually slow mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was purified from the Sarkosyl-insoluble pellet of Alzheimer's disease brain homogenates. Such species tau (PHF-tau) are considered to construct framework sulfate-soluble form paired helical filaments (PHF). Detailed comparison peptide maps PHF-tau and normal before after dephosphorylation pointed three anomalously eluted peaks which contained abnormally phosphorylated peptides, residues 191-225,...
A method is described for the partial purification of paired helical filaments that accumulate progressively in human neurons Alzheimer's disease (senile dementia). Paired have unusual solubility characteristics, including insolubility sodium dodecyl sulfate, urea, reducing agent, and guanidine, which prevent analysis their molecular composition by gel electrophoresis. The appear to contain covalent bonds other than disulfide, cross-link individual into a rigid intracellular polymer. Thus,...
Collapsin response mediating protein‐2 (CRMP2) has been identified as an intracellular protein Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin‐dependent kinase 5 (Cdk5) and glycogen synthase 3β (GSK3β) plays critical role in Sema3A signalling. vitro assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3β did not induce any phosphorylation of CRMP2. Phosphorylation by was exclusively observed Cdk5‐phosphorylated CRMP2, but barely CRMP2T509A....
γ-Cleavage of β-amyloid precursor protein (APP) in the middle cell membrane generates amyloid β (Aβ), and ϵ-cleavage, ∼10 residues downstream γ-cleavage site, releases APP intracellular domain (AICD). A significant link between generation Aβ AICD failure to detect AICD41-99 led us hypothesize that ϵ-cleavage longer Aβs, which are then processed Aβ40/42. Using newly developed gel systems an N-end-specific monoclonal antibody, we have identified Aβs (Aβ1-43, Aβ1-45, Aβ1-46, Aβ1-48) within...
Tau proteins are a class of low molecular mass microtubule-associated that specifically expressed in the nervous system. A cDNA clone adult rat tau was isolated and sequenced. To analyze functions vivo, we carried out transfection experiments. fibroblast cell line, which transfected with cDNA, three bands tau, while six were brain. After dephosphorylation, one disappeared, demonstrating directly phosphorylation involved multiplicity tau. Morphologically, observed thick bundle formation...
Paired helical filaments (PHF) are unusual neuronal fibers which accumulate progressively in the brain Alzheimer's disease (AD). The insolubility of PHF various kinds solvents enabled us to obtain highly purified PHF, but prevented application conventional analytical methods identify their components. Here we report that antibodies against recognize tau protein, a brainspecific microtubule-associated suggesting portion is protein.
Abstract The chronological relationship regarding deposition of amyloid β protein (Aβ) species, Aβ40 and Aβ42(43), was investigated in 16 brains from Down syndrome patients aged 31 to 64 years. frontal cortex probed with two end‐specific monoclonals that recognize or Aβ42(43). All senile plaques detected an authentic monoclonal were also Aβ42(43) positive, but only a varying proportion positive. In young (≤ 50 years old) there many Aβ42(43)‐positive, Aβ40‐negative diffuse plaques, few...
Amyloid β-peptide (Aβ) is known to accumulate in senile plaques of Alzheimer's disease (AD) patients and now widely believed play a major role the disease. Two populations peptides occur terminating either at amino acid 40 or 42 (Aβ1–40 Aβ1–42). Alternative N-terminal cleavages produce additional heterogeneity (Aβ<i>x</i>-40 Aβ<i>x</i>-42). Peptides are be player sporadic AD as well familial (FAD). Whereas cellular mechanism for generation Aβ understood, very little about cleavage after 42....
Several lines of evidence suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression Alzheimer's disease (AD). Amyloid beta-protein (Abeta) composes senile plaques, a major neuropathological hallmark AD, considered to have causal role AD. Thus, we studied effect on Abeta metabolism within cell. Here, report induced by H(2)O(2) (100-250 microM) caused an increase levels intracellular human neuroblastoma SH-SY5Y cells. Treatment with 200 microM significant...
The intramembrane cleavage of β-amyloid precursor protein by γ-secretase is the final step in generation amyloid β-protein. A 59- or 57-residue C-terminal fragment called CTFγ produced concomitantly. Putative generated rat brain membrane preparations was purified and sequenced. Instead CTFγ, shorter 50- 49-residue fragments were identified. In addition, we found similar precursor-like proteins 1 2; these also cleaved at corresponding sites. This newly identified occurs a site two to five...
Fetal tau and in paired helical filaments show similar immunoreactivities with several phosphorylation-dependent filament-polyclonals monoclonals, suggesting that the two molecules share distinct phosphorylated epitopes. To make clear similarities differences between two, we have undertaken work to identify vivo phosphorylation sites fetal rat tau. We approached this problem by identifying phosphopeptides means of mass spectrometry sequencing those after modification ethanethiol. Although...