Kazuhiro Hasegawa

ORCID: 0000-0003-3113-4522
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About
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Research Areas
  • Alzheimer's disease research and treatments
  • Amyloidosis: Diagnosis, Treatment, Outcomes
  • Protein Structure and Dynamics
  • Sirtuins and Resveratrol in Medicine
  • Prion Diseases and Protein Misfolding
  • Crystallization and Solubility Studies
  • Cholinesterase and Neurodegenerative Diseases
  • Spine and Intervertebral Disc Pathology
  • Autophagy in Disease and Therapy
  • Adenosine and Purinergic Signaling
  • Enzyme Structure and Function
  • Adipose Tissue and Metabolism
  • Hormonal Regulation and Hypertension
  • Drug Transport and Resistance Mechanisms
  • Advanced Glycation End Products research
  • Metabolism, Diabetes, and Cancer
  • Oral and Maxillofacial Pathology
  • Metabolism and Genetic Disorders
  • Biochemical effects in animals
  • Renal Diseases and Glomerulopathies
  • Dialysis and Renal Disease Management
  • Salivary Gland Tumors Diagnosis and Treatment
  • Analytical Chemistry and Chromatography
  • Diet and metabolism studies
  • Phytoestrogen effects and research

Tokushima University
1988-2024

Tokushima University Hospital
2024

Keio University
2014-2023

Tachikawa Hospital
2023

Shimane University
2023

Tokyo Dental College
2023

Tokuyama (Japan)
2023

Tokyo Dental College Ichikawa General Hospital
2022

University of Fukui
2007-2019

Nihon University
2005-2018

Abstract Inhibition of the accumulation amyloid β‐peptide (Aβ) and formation β‐amyloid fibrils (fAβ) from Aβ, as well destabilization preformed fAβ in central nervous system, would be attractive therapeutic targets for treatment Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) wine‐related polyphenols inhibit Aβ(1–40) Aβ(1–42) destabilize fAβ(1–40) fAβ(1–42) dose‐dependently vitro. Using fluorescence spectroscopic analysis with thioflavin T electron...

10.1002/jnr.20025 article EN Journal of Neuroscience Research 2004-02-13

Abstract Cerebral deposition of amyloid β‐peptide (Aβ) in the brain is an invariant feature Alzheimer's disease (AD). A consistent protective effect wine consumption on AD has been documented by epidemiological studies. In present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine effects wine‐related polyphenols (myricetin, morin, quercetin, kaempferol (+)‐catechin (–)‐epicatechin) formation, extension, destabilization β‐amyloid fibrils (fAβ) at pH...

10.1046/j.1471-4159.2003.01976.x article EN Journal of Neurochemistry 2003-09-12

Real-time monitoring of fibril growth is essential to clarify the mechanism amyloid formation. Thioflavin T (ThT) a reagent known become strongly fluorescent upon binding fibrils. Here, we show that, by ThT fluorescence with total internal reflection microscopy (TIRFM), fibrils औ2-microgobulin (औ2-m) can be visualized without requiring covalent labeling. One advantages TIRFM would that selectively monitor lying along slide glass, so obtain exact length This method was used follow kinetics...

10.1074/jbc.c300049200 article EN cc-by Journal of Biological Chemistry 2003-05-01

Study Design. Cross-sectional regional bone mineral density of the pedicle was measured by peripheral quantitative computed tomography. Biomechanical tests were performed to clarify role in screw stability. Objectives. To identify structural characteristics that supports stability and differences these between normal osteoporotic vertebrae. Summary Background Data. The is an essential component many systems used align spine. contribution stability, however, has not been fully investigated....

10.1097/00007632-199711010-00007 article EN Spine 1997-11-01

Abstract Iron as well aluminum is reported to accumulate in neurons with neurofibrillary tangles (NFTs) of Alzheimer's disease (AD) brain. Previously we demonstrated that (III) shows phosphate‐dependent binding hyperphosphorylated τ (PHFτ), the major constituent NFTs, thereby inducing aggregation PHFτ. Herein report iron can also induce soluble Importantly, for PHFτ occur, oxidized state essential since reduced (II) lacks such ability. Furthermore, (III)‐induced reversed by reducing (II)....

10.1046/j.1471-4159.2002.t01-1-01061.x article EN Journal of Neurochemistry 2002-09-01

10.1016/j.bbadis.2004.06.008 article EN publisher-specific-oa Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2004-07-13

The authors wish to make a correction the above article that was published in J. Neurochem. 82, pp. 11371147 . following sentence appeared Materials and methods section on 1139 fifth paragraph: ‘The epitope tag referred as BE7 consists of seven amino acid residues sequence SEPYHHW, which is derived from VP2 protein human parvovirus B19. correct should read follows. SQPYHHW,

10.1046/j.1471-4159.2002.01061.x article EN Journal of Neurochemistry 2003-03-12

A fundamental question about the early pathogenesis of Alzheimer's disease (AD) concerns how toxic aggregates amyloid beta protein (Abeta) are formed from its nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound Abeta (GAbeta) is involved in process. now examined this possibility using a novel monoclonal antibody raised against GAbeta purified an AD brain. Here, we report has conformation distinct and initiates aggregation by acting as seed. Furthermore, generation...

10.1523/jneurosci.0861-04.2004 article EN cc-by-nc-sa Journal of Neuroscience 2004-05-19

Sirt1, a NAD-dependent protein deacetylase, is reported to regulate intracellular metabolism and attenuate reactive oxidative species (ROS)-induced apoptosis leading longevity acute stress resistance. We created transgenic (TG) mice with kidney-specific overexpression of Sirt1 using the promoter sodium-phosphate cotransporter IIa (Npt2) driven specifically in proximal tubules investigated role protection against kidney injury (AKI). also elucidated number or function peroxisome mitochondria...

10.1074/jbc.m109.067728 article EN cc-by Journal of Biological Chemistry 2010-02-06

We analyzed the interaction of two kinds amyloid β-peptides (Aβ), i.e., Aβ(1−42) and Aβ(1−40), in kinetics β-amyloid fibril (fAβ) formation vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. When 25 μM was incubated increasing concentrations amyloidogenic time to proceed equilibrium extended dose-dependently. A similar inhibitory effect observed when 45 Aβ(1−40) Aβ(1−42). On other hand, 50 nonamyloidogenic at molar ratio 10:1 or...

10.1021/bi991161m article EN Biochemistry 1999-11-01

In β2-microglobulin-related (Aβ2M) amyloidosis, partial unfolding of β2-microglobulin (β2-m) is believed to be prerequisite its assembly into Aβ2M amyloid fibrils in vivo. Although low pH or 2,2,2-trifluoroethanol at a concentration has been reported induce β2-m and subsequent fibril formation vitro, factors that them under near physiological conditions have not determined. Using fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, electron microscopy, we here show...

10.1021/bi049262u article EN Biochemistry 2004-08-01

How various anti-amyloidogenic compounds inhibit the formation of Alzheimer's β-amyloid fibrils (fAβ) from amyloid β-peptide (Aβ) and destabilize fAβ remains poorly understood. Using spectrophotometry, spectrofluorometry, atomic force microscopy, sodium dodecyl sulfate−polyacrylamide gel electrophoresis, surface plasmon resonance (SPR), we investigated effects five flavonoids on in vitro. Oxidized generally inhibited fAβ(1−40) significantly more potently than fresh compounds....

10.1021/bi061540x article EN Biochemistry 2007-01-25

Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+-dependent protein deacetylase silent mating type information regulation homolog 1 (Sirtuin-1; SIRT1) PT survival decreases. Therefore, we hypothesized that increased influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine LLC-PK1 cells a two-chamber system were treated the inhibitor...

10.1038/s41598-018-25054-y article EN cc-by Scientific Reports 2018-04-25

Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide S-adenosylhomocysteine. Recently, this enzyme has also been reported modulate hepatic nutrient metabolism, but its role in liver not fully elucidated. We developed transgenic mice overexpressing NNMT elucidate metabolism. When fed a high fat diet containing NAM, precursor for adenine dinucleotide (NAD)

10.1038/s41598-018-26882-8 article EN cc-by Scientific Reports 2018-05-30

This study aimed to determine whether intra-articularly injected adipose-derived stem cells (ADSCs) inhibited articular cartilage degeneration during osteoarthritis (OA) development in a rabbit anterior cruciate ligament transection (ACLT) model. The paracrine effects of ADSCs on chondrocytes were investigated using co-culture system.ACLT was performed both knee joints 12 rabbits. isolated from the subcutaneous adipose tissue. with hyaluronic acid into left knee, and right knee. knees...

10.1186/s12891-015-0701-4 article EN cc-by BMC Musculoskeletal Disorders 2015-09-03

The role of gut microbiota in the progression chronic kidney disease (CKD) has not been fully elucidated.Renal failure was induced 6-week-old spontaneously hypertensive rats by 5/6 nephrectomy (Nx). We analyzed population to identify relevant species potentially involved inducing renal damage. Human colon Caco-2 cells were used delineate mechanism molecular changes Nx rats.Nx showed an increase Bacteroides (Bact) and a decrease Lactobacillus (Lact) compared with sham-operated rats. Lact, but...

10.1093/ndt/gfv353 article EN Nephrology Dialysis Transplantation 2015-10-20

Nicotinamide adenine dinucleotide (NAD+) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of NAD+ precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated NMN-producing enzyme phosphoribosyltransferase (Nampt) nephropathy. The expression Nampt PTs was downregulated streptozotocin (STZ)-treated mice when they exhibited This albuminuria ameliorated PT-specific...

10.1016/j.celrep.2019.03.024 article EN cc-by Cell Reports 2019-04-01

The activation of NAD+-dependent deacetylase, Sirt1, by the administration nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases.Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed effects on diabetic nephropathy (DN).At 14 after treatment period, attenuated increases in urinary albumin excretion without ameliorating hemoglobin A1c levels. Short-term mitigated mesangium expansion foot process effacement, while decreased Sirt1 expression...

10.1681/asn.2020081188 article EN Journal of the American Society of Nephrology 2021-04-01

Investigation of factors that modulate amyloid formation proteins is important to understand and mitigate amyloid-related diseases. To the role electrostatic interactions effect ionic cosolutes, especially anions, on formation, we have investigated salts such as NaCl, NaI, NaClO(4), Na(2)SO(4) fibril growth beta(2)-microglobulin, protein involved in dialysis-related amyloidosis. Under acidic conditions, these exhibit characteristic optimal concentrations where favored. The presence leads an...

10.1021/bi048029t article EN Biochemistry 2005-01-07
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