A5102983829- Alzheimer's disease research and treatments
- S100 Proteins and Annexins
- 14-3-3 protein interactions
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Drug Transport and Resistance Mechanisms
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Dementia and Cognitive Impairment Research
- Lipid Membrane Structure and Behavior
- Metabolomics and Mass Spectrometry Studies
- Cellular Mechanics and Interactions
- Neurobiology and Insect Physiology Research
- Aluminum toxicity and tolerance in plants and animals
- Glycosylation and Glycoproteins Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- RNA Research and Splicing
- Virology and Viral Diseases
- Amino Acid Enzymes and Metabolism
- Bioinformatics and Genomic Networks
Hokkaido University
2015-2024
National Institute of Advanced Industrial Science and Technology
2020-2023
Hokkaido Pharmaceutical University
2022
Tokyo Metropolitan Institute of Gerontology
2020
Institute of Neurobiology
2020
Syngeneic SL mice inoculated with murine myeloid leukemia cells (M1) all died of within 30 days. Treatment three times a week 12.5-50 pmol per mouse either 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form vitamin D3, or its synthetic analog, alpha-hydroxyvitamin alpha(OH)D3], considerably prolonged survival time M1 cells. alpha(OH)D3 was more effective than alpha,25(OH)2D3 in increasing mice. also increased nude The alpha(OH)[3H]D3 administered intraperitoneally to...
Actin is a major structural component of the cytoskeleton in eukaryotic cells, and filamentous actin (F-actin) forms variety types cellular structures. Many probes have been developed to visualize F-actin architectures cells. However, it known that double-stained images obtained by two different often show partial inconsistencies. While developing probes, we observed merged three distinct each labeled with fluorescent dye (red, green blue), enabled various be distinguished based on color....
Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting 1 (JIP1); however, the role of JIP1 in APP transport by neurons remains unclear. We performed a quantitative analysis to understand axonal transport. In JIP1-deficient neurons, we find that both fast velocity (∼2.7 μm/s) and high frequency (66%) anterograde cargo are impaired reduced (∼1.83 lower (45%). identified two novel elements linked function, located central region JIP1b, interact coiled-coil...
Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins, designated Alc(alpha), Alc(beta), and Alc(gamma). The Alcs express in neurons dominantly largely colocalize with the Alzheimer amyloid precursor protein (APP) brain. APP show an identical function as cargo receptor kinesin-1. Moreover, proteolytic processing Alc proteins appears highly similar to that APP. We found alpha-secretases ADAM 10 17 primarily cleave trigger subsequent secondary intramembranous cleavage...
The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by γ-secretase due to mutations presenilin 1 (PS1) gene. This misprocessing/alternative processing leads an increase in ratio level a minor reaction product (Aβ42) that major (Aβ40). Although no PS1 are present, altered Aβ42/40 ratios also observed sporadic (SAD), and these apparently reflect deposition Aβ42 as amyloid.Using...
X11-family proteins, including X11, X11-like (X11L) and 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) regulate APP metabolism. Both X11 X11L are expressed specifically in brain, while X11L2 is ubiquitously. predominantly excitatory neurons, contrast which strongly inhibitory neurons. In vivo gene-knockout studies targeting X11L, or both, transgenic mice have reported that proteins suppress amyloidogenic processing endogenous mouse ectopic human with one...
Generation of amyloid-β peptides (Aβs) by proteolytic cleavage the protein precursor (AβPP), especially increased production Aβ 42 /Aβ 43 over 40 , and their aggregation as oligomers plaques, represent a characteristic feature Alzheimer’s disease (AD). In familial AD (FAD), altered originates from specific mutations AβPP or presenilins 1/2 (PS1/PS2), catalytic subunits γ-secretase. sporadic AD, origin Aβs remains unknown. We hypothesize that ‘human chemical exposome’ contains products able...
Amyloid β-proteins (Aβs) Aβ1-42 and Aβ1-43 are converted via two product lines of γ-secretase to Aβ1-38 Aβ1-40. This parallel stepwise processing model predicts that Aβ1-43, Aβ1-40 proportional each other, respectively. To obtain further insight into the mechanisms parenchymal Aβ deposition, these four species were quantified in insoluble fractions human brains (Brodmann areas 9 11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays. With advancing...
Amyloid β-precursor protein (APP) is primarily cleaved by α- or β-secretase to generate membrane-bound, C-terminal fragments (CTFs). In turn, CTFs are potentially subject a second, intramembrane cleavage γ-secretase, which active in lipid raft-like membrane microdomain. Mature APP (N- and O-glycosylated APP), the actual substrate of these secretases, phosphorylated at cytoplasmic residue Thr668 this phosphorylation changes overall conformation domain APP. We found that nonphosphorylated...
Abstract We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3‐Alcβ37 is generated from the neuronal protein alcadein β through cleavage of γ‐secretase, similar to generation amyloid (Aβ) derived Aβ‐protein precursor/APP. Neurotoxicity by Aβ oligomers (Aβo) prime cause prior loss brain function in AD. found that and its shorter p3‐Alcβ9‐19 enhanced mitochondrial activity neurons protected against Aβo‐induced toxicity. This due suppression Aβo‐mediated excessive...
We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1 H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). examined posterior cingulate gyri 228 subjects usin
The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity cytochrome c oxidase (COX/complex IV) decreases patients Alzheimer's disease (AD). COX, a inner membrane protein complex that contains heme, plays an role electron transport chain generates ATP. Heme synthesis begins 5-aminolevulinic acid (5-ALA) mitochondria. 5-ALA synthetase is rate-limiting enzyme heme synthesis, suggesting...
Proteolytic cleavage of the amyloid-β protein precursor (AβPP) by secretases leads to extracellular release (Aβ) peptides. Increased production Aβ42 over Aβ40 and aggregation into oligomers plaques constitute an Alzheimer's disease (AD) hallmark. Identifying products 'hum chemical exposome' (HCE) able induce may be a key understanding some initiating causes AD generate non-genetic, chemically-induced animal models. A cell model was used screen HCE libraries for inducers. Out 3500+ compounds,...
Alzheimer's disease (AD) is a very common neurodegenerative disorder, chiefly caused by increased production of neurotoxic β-amyloid (Aβ) peptide generated from proteolytic cleavage protein precursor (APP). Except for familial AD arising mutations in the APP and presenilin (PSEN) genes, molecular mechanisms regulating amyloidogenic processing are largely unclear. Alcadein α/calsyntenin1 (ALCα/CLSTN1) neuronal type I transmembrane that forms complex with APP, mediated adaptor X11-like (X11L...
Atypical ocular bobbing resulted from an intentional poisoning dimpylate (Diazinon), organophosphate compound. In discussing the possible foci and mechanism for atypical associated with acute poisoning, we suggest acetylcholine as a neurotransmitter substance within motor pathway. A literature review has not shown any previous reported cases this sign.
Various membrane proteins are shed by proteinases, constitutively and/or when stimulated external signals. While the physiological significance of signal-induced cleavages has been intensely investigated, relatively little is known about function constitutive cleavages. Alcadeinα (Alcα; also called Calsyntenin-1) an evolutionarily conserved type I single-pass transmembrane protein that binds to kinesin-1 light chain (KLC) activate kinesin-1's transport Alcα-containing vesicles. We found Alcα...
Background Alcadein proteins (Alcs; Alcα, Alcβand Alcγ) are predominantly expressed in neurons, as is Alzheimer's β-amyloid (Aβ) precursor protein (APP). Both Alcs and APP cleaved by primary α- or β-secretase to generate membrane-associated C-terminal fragments (CTFs). Alc CTFs further γ-secretase secrete p3-Alc peptide along with the release of intracellular domain fragment (Alc ICD) from membrane. In case APP, CTFβ initially at ε-site (AICD) consequently γ-site determined, which Aβ...
In neurons, amyloid β-protein precursor (APP) is transported by binding to kinesin-1, mediated JNK-interacting protein 1b (JIP1b), which generates the enhanced fast velocity (EFV) and efficient high frequency (EHF) of APP anterograde transport. Previously, we showed that EFV requires conventional interaction between JIP1b C-terminal region kinesin light chain 1 (KLC1) tetratricopeptide repeat, whereas EHF a novel central coiled-coil domain KLC1. We found phosphorylatable Thr466 KLC1...
Abstract Background Alcadein α (Alc ) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor (APP). Successive cleavage of APP by β- and γ-secretases generates aggregatable peptide (Aβ), while or Alc α- non-aggregatable p3 p3-Alc peptides. Aβ can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing in CSF some patients sporadic mild cognitive impairment (MCI) AD (SAD). Results Using sandwich enzyme-linked...
Alcadein α (Alcα) is a major cargo of kinesin-1 that subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) kinesin light chain (KLC), which activate recruit Alcα cargo. We found phosphorylation three serine residues acidic region between two WD required for interaction with KLC. Phosphorylation these may alter disordered structure induce direct association...
p3-Alcα is a metabolic fragment of Alcadeinα (Alcα). Similar to the generation p3 from amyloid-β protein precursor (AβPP) processing, Alcα cleaved by α- and γ-secretases, leading secretion peptides into cerebrospinal fluid (CSF). also detected in plasma, similar (Aβ), which AβPP amyloidogenic β- γ-secretases. Because non-aggregatable stable peptide, unlike aggregatable Aβ metabolically labile AβPP, changes quality and/or quantity CSF plasma are expected be marker for assessing alteration...