A5011533166- Amyloidosis: Diagnosis, Treatment, Outcomes
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Antimicrobial Peptides and Activities
- Protein Kinase Regulation and GTPase Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Cell Adhesion Molecules Research
- Invertebrate Immune Response Mechanisms
- Proteins in Food Systems
- Biochemical and Structural Characterization
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Drug Transport and Resistance Mechanisms
- Biotin and Related Studies
- Glycosylation and Glycoproteins Research
- Pharmacological Effects of Natural Compounds
- Amino Acid Enzymes and Metabolism
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
University of Toyama
2016-2025
Nagahama Institute of Bio-Science and Technology
2024
Ibaraki University
2013
Tohoku Medical and Pharmaceutical University
2001-2012
Tokushima University
2011
Chinese University of Hong Kong
2011
University of Hong Kong
2011
National Institute for Biological Standards and Control
2011
Toyama Institute of Health
2010
National Institute of Infectious Diseases
2010
Brain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins by direct interaction triggers an innate immune response activating cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) pathway. Tamoxifen-inducible microglia-specific depletion PQBP1 primary culture vitro mouse brain vivo shows that is essential for sensing-tau to induce...
Amyloid-β, tau, and α-synuclein, or more specifically their soluble oligomers, are the aetiologic molecules in Alzheimer's disease, tauopathies, α-synucleinopathies, respectively. These proteins have been shown to interact accelerate each other's pathology. Clinical studies of amyloid-β-targeting therapies disease revealed that treatments after onset little benefit on patient cognition. findings prompted us explore a preventive medicine which is orally available, has few adverse effects,...
Amyloid fibril formation is associated with protein misfolding disorders, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Familial amyloid polyneuropathy (FAP) a hereditary disease caused by point mutation of the human plasma protein, transthyretin (TTR), which binds transports thyroxine (T4). TTR variants contribute to pathogenesis amyloidosis forming fibrils in extracellular environment. A recent report showed that epigallocatechin...
Lewy bodies, mainly composed of α-synuclein (αS), are pathological hallmarks Parkinson's disease and dementia with bodies. Epidemiological studies showed that green tea consumption or habitual intake phenolic compounds reduced risk. We previously reported inhibited αS fibrillation destabilized preformed fibrils. Cumulative evidence suggests low-order oligomers neurotoxic critical species in the pathogenesis α-synucleinopathies. To develop modifying therapies for α-synucleinopathies, we...
Death-associated protein kinase 1 (DAPK1) is a 160 kDa serine/threonine that belongs to the Ca(2+)/calmodulin-dependent subfamily. DAPK1 possible target for treatment of acute ischemic stroke and endometrial adenocarcinomas. In present study, we investigated binding characteristics 17 natural flavonoids using 1-anilinonaphthalene-8-sulfonic acid competitive assay revealed morin was strongest binder among selected compounds. The crystallographic analysis 7 flavonoid complexes...
Microtubule-associated protein (MAP) light chain 3 (LC3) is a human homologue of yeast Apg8/Aut7/Cvt5 (Atg8), which essential for autophagy. MAP-LC3 cleaved by cysteine protease to produce LC3-I, located in cytosolic fraction. turn, converted LC3-II through the actions E1- and E2-like enzymes. covalently attached phosphatidylethanolamine on its C terminus, it binds tightly autophagosome membranes. We determined solution structure LC3-I found that divided into N- C-terminal subdomains....
Fourier‐transform infrared spectroscopy (FT‐IR) was applied to examine relationships between the type of coordination and COO − antisymmetric symmetric stretches groups in Ca 2+ ‐binding site bovine α‐lactalbumin. The peaks at 1593, 1578, 1425, 1403 cm −1 were assigned Asp‐82, 87, 88 coordinating pseudo bridging mode, according results X‐ray crystallography. bands due quite similar each other α‐lactalbumin EDTA which is model compound for state.
Mass spectrometric analyses are valuable for detection of transthyretin (TTR) variants, which cause familial amyloidotic polyneuropathy (FAP). However, those methods require an immunoprecipitation step with anti-TTR antibody and not suitable quantitative detection. We investigated the usefulness SELDI-TOF mass spectrometry (MS) without step.We used ProteinChips chromatographic capture formats to detect TTRs. attempted correlate intensity mixed samples amyloidogenic TTR (ATTR) V30M wild-type...
Transthyretin (TTR) is a homotetrameric serum protein associated with amyloidoses such as familial amyloid polyneuropathy and senile systemic amyloidosis. The fibril formation of TTR can be inhibited through stabilization the tetramer by binding small molecules. In this study, we examined inhibitory potency caffeic acid phenethyl ester (CAPE) its derivatives. Thioflavin T assay showed that CAPE suppressed TTR. Comparative analysis potencies revealed ferulate was most potent among selected...
Transthyretin (TTR), a plasma protein, undergoes transformation into amyloid fibers, leading to ATTRv amyloidosis, disease characterized by organ deposition of TTR fibrils and subsequent failure. Developing compounds that bind kinetically stabilize is crucial strategy in the treatment amyloidosis. In this study, we narrowed 651 pesticide-related down 14 possible binders through silico screening; vitro analysis revealed 7 them exhibited fibril formation inhibition activity. The herbicide...
Novel surface plasmon resonance-based biosensor assays for the bioeffect-related screening of chemicals with thyroid-disrupting activity are described. Two thyroid transport proteins (TPs), thyroxine binding globulin (TBG) and recombinant transthyretin (rTTR), were applied in an inhibition assay format a Biacore 3000 using CM5 chips coated l-thyroxine (T4), main hormone system. Assay conditions optimized natural hormones, known disruptors structurally related compounds selected as model to...
D-Serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)–type glutamate receptor in central nervous system and its synthesis catalyzed by serine racemase (SR). Recently, NMDA has been found to be expressed keratinocytes (KCs) skin involved regulation KC growth differentiation. However, localization role SR remain unknown. Here, using SR-knockout (SR-KO) mice as control, we demonstrated protein granular cornified layer epidermis wild-type (WT) appearance confluent WT KCs. We...
Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl (IPP) and dimethylallyl to FPP is known be a molecular target osteoporosis drugs, such as risedronate (RIS), which nitrogen-containing bisphosphonate. The protonation states hydration structure RIS bound FPPS were determined by neutron protein crystallography, allows direct visualization hydrogens deuteriums. analysis revealed that phosphate groups fully deprotonated with abnormally decreased pKa, roles E93 D264...
Big defensin is a 79-residue peptide derived from hemocytes of the Japanese horseshoe crab. It has antimicrobial activities against Gram-positive and -negative bacteria. The amino acid sequence big can be divided into an N-terminal hydrophobic half C-terminal cationic half. Interestingly, trypsin cleaves two fragments, which are responsible for activity bacteria, respectively. To explore mechanism defensin, we determined solution structure mature performed titration experiment with DPC...