Tokyo Metropolitan Institute of Medical Science
Tokyo Metropolitan Institute of Medical Science
PeptiDream Inc. and Tokyo Metropolitan Institute of Medical Science | Date: 2017-08-30
Object of the present invention is to provide a hemagglutinin-binding peptide producing an anti-influenza virus effect higher than that of existing peptides. The present invention provides, for example, a hemagglutinin-binding peptide comprising a polypeptide having any of the following amino acid sequences (i) to (iv):(i) Thr-MeGly-Asp-MePhe-MePhe-Ser-MeSer-His-Tyr-Thr-Val-Pro-Arg (SEQ ID NO:1);(ii) Arg-Val-Ser-MePhe-Thr-Tyr-MePhe-MeSer-Tyr-Thr-Pro-Ser (SEQ ID NO: 2);(iii) an amino acid sequence with deletions, additions, or substitutions of one or several amino acids in SEQ ID NO: 1 or 2; and(iv) an amino acid sequence having 90% or more sequence identity to that of SEQ ID NO: 1 or 2.
Tokyo Metropolitan Institute of Medical Science | Date: 2017-10-11
A non-human mammal and an offspring thereof, obtainable by a somatic cell nuclear transfer method using a nucleus of a CD4-positive T cell as a nuclear donor. The non-human mammal of the present invention surely and efficiently shows allergic reactions specific to various antigens that are shown to have associations with an immune allergic disease, such as mites and cedar pollens, so that the non-human mammal can be suitably used as the developmental models of allergic diseases for studies of various diseases by studying or pursuing possibilities of applications to the diseases.
Tokyo Metropolitan Institute of Medical Science, National Institutes Of Biomedical Innovation and The Chemo Sero Therapeutic Research Institute | Date: 2017-09-20
The present invention can induce stronger cellular immunity to hepatitis C and provide a treatment means and a prevention means that are effective in completely eliminating the hepatitis C virus (HCV). Provided is a pharmaceutical composition for the treatment and/or prevention of hepatitis C, said composition comprising a recombinant vaccinia virus (a) and a recombinant vector (b) and characterized in that after one of the recombinant vaccinia virus (a) and the recombinant vector (b) is administered for initial immunity, the other is administered for additional immunity. The recombinant vaccinia virus (a) contains an expression promoter and all or a portion of the cDNA of the HCV genome. The recombinant vector (b) contains an expression promoter and all or a portion of the cDNA of the HCV (where the cDNA contained in the recombinant vector (b) has a different base sequence than that included in the recombinant vaccinia virus (a)).
Sato A.,Tokyo Metropolitan Institute of Medical Science
CNS and Neurological Disorders - Drug Targets | Year: 2016
Mammalian target of rapamycin (mTOR) is a key regulator in various cellular processes, including cell growth, gene expression, and synaptic functions. Autism spectrum disorder (ASD) is frequently accompanied by monogenic disorders, such as tuberous sclerosis complex, phosphatase and tensin homolog tumor hamartoma syndrome, neurofibromatosis 1, and fragile X syndrome, in which mTOR is hyperactive. Mutations in the genes involved in the mTOR-mediated signaling pathway have been identified in some cases of syndromic ASD. Evidences indicate a pathogenic role for hyperactive mTOR-mediated signaling in ASD associated with these monogenic disorders, and mTOR inhibitors are a potential pharmacotherapy for ASD. Abnormal synaptic transmission through metabotropic glutamate receptor 5 may underlie in a part of ASD associated with hyperactive mTOR-mediated signaling. In this review, the relationship between mTOR and ASD is discussed. © 2016 Bentham Science Publishers.
Maeda N.,Tokyo Metropolitan Institute of Medical Science
Frontiers in Neuroscience | Year: 2015
Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major constituents of the extracellular matrix and the cell surface in the brain. Proteoglycans bind with many proteins including growth factors, chemokines, axon guidance molecules, and cell adhesion molecules through both the glycosaminoglycan and the core protein portions. The functions of proteoglycans are flexibly regulated due to the structural variability of glycosaminoglycans, which are generated by multiple glycosaminoglycan synthesis and modifying enzymes. Neuronal cell surface proteoglycans such as PTP?, neuroglycan C and syndecan-3 function as direct receptors for heparin-binding growth factors that induce neuronal migration. The lectican family, secreted chondroitin sulfate proteoglycans, forms large aggregates with hyaluronic acid and tenascins, in which many signaling molecules and enzymes including matrix proteases are preserved. In the developing cerebrum, secreted chondroitin sulfate proteoglycans such as neurocan, versican and phosphacan are richly expressed in the areas that are strategically important for neuronal migration such as the striatum, marginal zone, subplate and subventricular zone in the neocortex. These proteoglycans may anchor various attractive and/or repulsive cues, regulating the migration routes of inhibitory neurons. Recent studies demonstrated that the genes encoding proteoglycan core proteins and glycosaminoglycan synthesis and modifying enzymes are associated with various psychiatric and intellectual disorders, which may be related to the defects of neuronal migration. © 2015 Maeda.
Mizushima N.,Tokyo Medical and Dental University |
Komatsu M.,Tokyo Metropolitan Institute of Medical Science
Cell | Year: 2011
Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. © 2011 Elsevier Inc.
Hasegawa M.,Tokyo Metropolitan Institute of Medical Science
Acta neuropathologica communications | Year: 2014
BACKGROUND: α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, so-called α-synucleinopathies. Recent studies revealed that intracerebral injection of recombinant α-synuclein fibrils into wild-type mouse brains induced prion-like propagation of hyperphosphorylated α-synuclein pathology. However, the propagation mechanisms of α-synuclein have not been fully elucidated.RESULTS: In this study, in order to establish where and how α-synuclein pathology propagates, we injected recombinant mouse α-synuclein fibrils into three different brain areas (substantia nigra, striatum, and entorhinal cortex) of wild-type mice and compared the resulting distributions of α-synuclein pathology at 1 month after injection. Distinct patterns of pathology were observed in mice injected at the different sites. Within one month after injection, the pathology had spread to neurons in areas far from the injection sites, especially areas with direct neural connections to the injection sites. Surprisingly, phosphorylated tau and TDP-43 pathologies were also observed in mice injected with α-synuclein fibrils into striatum and entorhinal cortex at one month after injection. Phosphorylated tau and TDP-43 were accumulated in dot-like inclusions, but these were rarely colocalized with α-synuclein pathology. It seems that accumulation of α-synuclein has a synergistic effect on tau and TDP-43 aggregation. Additionally, intracerebral injection with sarkosyl-insoluble fraction prepared from wild-type mice injected synthetic α-synuclein fibrils can also induce phosphorylated α-synuclein pathology in wild-type mice.CONCLUSIONS: Our data indicate that α-synuclein aggregation spread by prion-like mechanisms through neural networks in mouse brains.
Akiyama H.,Tokyo Metropolitan Institute of Medical Science
Acta neuropathologica communications | Year: 2014
BACKGROUND: Tangle-predominant dementia (TPD) is characterized neuropathologically by numerous neurofibrillary tangles in the limbic areas with no or occasional senile plaques throughout the brain. TPD is an under-recognized disease, while it is a common cause of dementia in those over 80 years of age. In the present study, we describe hyperphosphorylated tau (tau) accumulation in the nucleus accumbens (Acb) in patients with TPD.RESULTS: We investigated immunohistochemically the brain tissues from 7 patients with TPD, 22 with Alzheimer disease (AD) and 11 non-demented aged subjects. In the Acb of all 7 TPD patients, a considerable number of tau positive neurons were found together with many neuropil threads. The tau deposits in the Acb were labeled with all the anti-tau antibodies used in the present study. They included conformational change-specific, phosphorylation-specific and phosphorylation-independent antibodies. The Acb consists of the predominant medium-sized neurons with a small number of large neurons. Both the cell types were affected by tau pathology in TPD. Tau accumulation in the majority of such neurons appeared to be pretangle-like, diffuse deposits with only occasional paired helical filament formation. Tau positive neurons were also found in the Acb in some AD and non-demented aged subjects but much fewer in the majority of cases. The immunoblot analyses of fresh frozen samples of the Acb and parahippocampal cortex from 3 TPD and 3 AD patients revealed that the insoluble tau in the Acb was a mixture of the 3- and 4-repeat isoforms.CONCLUSIONS: To our knowledge, this is the first report on the occurrence of tau accumulation in the Acb in TPD. The Acb receives direct and massive projections from the hippocampal CA1 and subiculum where neurofibrillary tangles are known to occur more frequently in TPD than in AD. The prevalence of abnormal tau accumulation in the Acb in TPD may support the idea that abnormal tau aggregation propagates via neural circuits. In all but one TPD cases used in this study, delusion was a consistent clinical feature. Whether the Acb tau accumulation is related to the psychiatric symptoms in TPD may be an issue for further investigation.
Tokyo Metropolitan Institute of Medical Science | Date: 2016-09-21
An object of the present invention is to provide a method for efficiently identifying a polyubiquitinated substrate which is generally not easily identified. The method for identifying a polyubiquitinated substrate includes (1) a step of expressing a trypsin-resistant polyubiquitin chain-binding protein and a ubiquitin ligase in a cell, (2) a step of isolating a complex that contains the trypsin-resistant polyubiquitin chain-binding protein from the cell having undergone the step (1), (3) a step of subjecting the complex isolated by the step (2) to trypsin digestion, and (4) a step of identifying a peptide that has a ubiquitination site from a digested material obtained by the step (3).
Tokyo Metropolitan Institute of Medical Science | Date: 2016-03-09
The present invention has an objective of evaluating a motor function of a subject with a neurodegenerative disease with high accuracy using a motor function analysis system that utilizes a wrist joint movement of the subject. The motor function analysis system 1 of the present invention comprises: a display unit 3 for displaying image information including a moving target image and a cursor image 11 for tracking the target image; a moving unit 4 used by the subject to move the cursor image 11; and an analyzer 7 for detecting the tracking status of the target image tracked by the cursor image and analyzing the frequency of the movement components contained in the tracking status.