A5103196376- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Pluripotent Stem Cells Research
- Prion Diseases and Protein Misfolding
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- 3D Printing in Biomedical Research
- Functional Brain Connectivity Studies
- Single-cell and spatial transcriptomics
- Biochemical effects in animals
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Adrenal and Paraganglionic Tumors
- Histone Deacetylase Inhibitors Research
- Medicinal Plants and Neuroprotection
- Medical and Biological Ozone Research
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Machine Learning in Bioinformatics
Keio University
2018-2024
Gladstone Institutes
2011-2024
University of California, San Francisco
2011-2024
Keio University Hospital
2024
Fujifilm (Japan)
2024
Hiroshima University
2024
RIKEN Center for Brain Science
2003-2018
RIKEN
2006-2010
Tokyo Metropolitan Geriatric Hospital
2007
Tokyo Institute of Technology
2006-2007
Neurofibrillary tangles (NFTs) are pathological hallmarks of several neurodegenerative disorders, including Alzheimer's disease (AD). NFTs composed microtubule-binding protein tau, which assembles to form paired helical filaments (PHFs) and straight filaments. Here we show by atomic force microscopy that AD brain tissue in vitro tau granular fibrillar aggregates. CD spectral analysis immunostaining with conformation-dependent antibodies indicated may undergo conformational changes during...
Abstract Abnormal accumulation of tau as filamentous structures is a neuropathological hallmark neurodegenerative diseases referred to tauopathies. Little known about the role native cysteine residues in assembly because their substitution with other amino acids has no effect on filament morphology. To understand process involved oligomerization, we analysed both heparin‐induced different forms recombinant human and from COS‐7 cells transiently expressing constructs. Here, demonstrated that...
Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one earliest pathological hallmarks patients with Alzheimer's disease (AD). It can occur before significant Aβ deposition and appears to "spread" into anatomically connected brain regions. To determine whether this early-stage pathology sufficient cause progression cognitive decline experimental models, we overexpressed mutant human (hTauP301L) predominantly layer II/III neurons mouse EC. Cognitive functions remained...
A152T-variant human tau (hTau-A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau-A152T or wild-type hTau (hTau-WT), we find age-dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in mice. However, overexpression either species enhances responses to electrical stimulation synaptic inputs an epileptogenic chemical. have higher protein/mRNA ratios brain, suggesting...
Abstract Neurofibrillary tangles, composed of hyperphosphorylated tau fibrils, are a pathological hallmark Alzheimer’s disease; the neurofibrillary tangle load correlates strongly with clinical progression disease. A growing body evidence indicates that oligomer formation precedes appearance tangles and contributes to neuronal loss. Here we show can be inhibited by compounds whose chemical backbone includes 1,2-dihydroxybenzene. Specifically, demonstrate 1,2-dihydroxybenzene-containing bind...
Because the deposition of β-amyloid protein (Aβ) is a consistent pathological hallmark Alzheimer's disease (AD) brains, inhibition Aβ generation, prevention fibril formation, or destabilization preformed fibrils would be attractive therapeutic strategies for treatment AD. We examined effects several medicinal herbs used in traditional Chinese medical formulae on formation and by using thioflavin T binding assay, atomic force microscopic imaging, electrophoresis. Our study demonstrates that...
Abstract The deposition of amyloid β (Aβ) protein is a consistent pathological hallmark Alzheimer’s disease (AD) brains; therefore, inhibition Aβ fibril formation and destabilization pre‐formed fibrils an attractive therapeutic preventive strategy in the development disease‐modifying drugs for AD. This study demonstrated that Paeonia suffruticosa , traditional medicinal herb, not only inhibited both 1–40 1–42 but it also destabilized concentration‐dependent manner. Memory function was...
Neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau, are hallmarks neurodegenerative diseases including Alzheimer disease (AD). In diseases, neuronal dysfunction due to loss and synaptic accompanies NFT formation, suggesting that a process associated with formation may be involved in dysfunction. To clarify the relationship between tau aggregation synapse loss, we compared two lines mice expressing human or without an aggregation-prone P301L mutation. transgenic (Tg)...
Alzheimer’s disease pathology is characterized by extracellular deposits of amyloid-β (Aβ) and intracellular inclusions hyperphosphorylated tau. Although genetic studies familial suggest a causal link between Aβ symptoms, the failure various Aβ-targeted strategies to slow or halt progression has led consideration idea that inhibition tau aggregation might be more promising therapeutic approach. Methylene blue (MB), which inhibits rescue memory deficits in mouse model tauopathy, however,...
Mutations in the microtubule-associated protein tau (MAPT) gene are known to cause familial frontotemporal dementia (FTD). The R406W mutation is a unique missense whose patients have been reported exhibit Alzheimer's disease (AD)-like phenotypes rather than more typical FTD phenotypes. In this study, we established patient-derived induced pluripotent stem cell (iPSC) models investigate pathology by mutation. We generated iPSCs from and isogenic lines using CRISPR/Cas9. were into cerebral...
Abstract Intracellular accumulation of filamentous tau proteins is a defining feature neurodegenerative diseases termed tauopathies . The pathogenesis remains largely unknown. Molecular chaperones such as heat shock (HSPs), however, have been implicated in well other characterized by the insoluble protein aggregates. To search for vivo evidence chaperone‐related metabolism, we analyzed human brains with varying degrees neurofibrillary tangle (NFT) pathology, defined Braak NFT staging....
The mechanism underlying plaque-independent neuronal death in Alzheimer disease (AD), which is probably responsible for early cognitive decline AD patients, remains unclarified. Here, we show that a toxic soluble Aβ assembly (TAβ) formed the presence of liposomes containing GM1 ganglioside more rapidly and to greater extent from hereditary variant-type ("Arctic") than wild-type Aβ.TAβ also through incubation with natural membranes prepared aged mouse brains ganglioside-dependent manner. An...
Abstract Background The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural in the brain. However, many iPSC-derived models established to date typically involve only a single type. These monoculture are inadequate accurately simulating brain environment, where multiple types interact. limited type diversity hinders accurate recapitulation phenotypes resulting from interactions between...
Etiological studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer's disease (AD). Biochemical analysis data on the effects Al, however, are inconsistent. Hence, pathological involvement Al in AD remains unclear. If is involved AD, then it reasonable to hypothesize be formation either amyloid plaques or neurofibrillary tangles (NFTs). Here, we investigated whether NFT by using vitro tau aggregation paradigm, a tau-overexpressing neuronal cell...
17β-Estradiol (E2) is a sex hormone that has been previously demonstrated to have neurotherapeutic effects on animal models of Alzheimer's disease (AD). However, clinical trials E2 replacement therapy for preventing AD onset yielded inconsistent results. Therefore, it imperative clarify the therapeutic human cells. In this study, we utilized induced pluripotent stem cells (iPSCs) derived from multiple donors explore in vitro model We conducted systematic review and meta-analysis using...
Human neural cell models derived from induced pluripotent stem cells (iPSCs) have been widely accepted to model various neurodegenerative diseases such as Alzheimer's disease (AD) in vitro. Although the most common sources of iPSCs are fibroblasts and peripheral blood mononuclear cells, collection these is invasive. To reduce donor's burden, we propose use urine-derived (UDCs), which can be obtained non-invasively a urine sample. However, UDCs elderly donors suffering age-related AD has not...
Sporadic Alzheimer's disease (sAD) is a neurodegenerative that has the highest prevalence among patients with dementia. The genetic risk factors for sAD are comprised of many single nucleotide polymorphisms (SNPs), as indicated by genome-wide association studies. Herein, we generated KEIOi005-A-induced pluripotent stem cell (iPSC) line from urine-derived cells (UDCs) mild (AD) patient multiple SNPs comprising T > C heterozygous APOE ε3/ε4 (rs429358), A G BIN1 (rs744373), and homozygous...