A5088123955- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Protein Kinase Regulation and GTPase Signaling
- Peripheral Neuropathies and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Myasthenia Gravis and Thymoma
- Endoplasmic Reticulum Stress and Disease
- Ion channel regulation and function
- Genetic Neurodegenerative Diseases
- Biochemical effects in animals
- Neurogenetic and Muscular Disorders Research
- Neurological disorders and treatments
- Cellular transport and secretion
- Nitric Oxide and Endothelin Effects
- Multiple Sclerosis Research Studies
- 14-3-3 protein interactions
San Francisco VA Medical Center
2024
University of California, San Francisco
2024
Sapporo Medical University
2014-2023
Sapporo Medical University Hospital
2023
Saiseikai Ibaraki Hospital
2023
Nerima General Hospital
2023
Sapporo University
2009-2022
Memorial Hospital
2022
Tohoku Medical Megabank Organization
2021
Tohoku University
2002-2021
Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and amino acid, nitrotyrosine in vulnerable neurons patients with Alzheimer disease (AD). To determine whether oxidative damage is early- or end-stage event the process neurodegeneration AD, investigated relationship between neuronal 8OHG histological clinical variables, i.e. amyloid-β (Aβ) plaques neurofibrillary tangles (NFT), as well duration dementia apolipoprotein E...
The finding that oxidative damage, including to nucleic acids, in Alzheimer's disease is primarily limited the cytoplasm of susceptible neuronal populations suggests mitochondrial abnormalities might be part spectrum chronic stress disease. In this study, we used situ hybridization DNA (mtDNA), immunocytochemistry cytochrome oxidase, and morphometry electron micrographs biopsy specimens determine whether there are their relationship damage marked by 8-hydroxyguanosine nitrotyrosine. We found...
Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathogenesis Alzheimer's disease (AD). Here we show signal transduction mechanism involved receptor-mediated protection against β-amyloid-enhanced glutamate neurotoxicity. Nicotine-induced was suppressed by an α7 receptor antagonist (α-bungarotoxin), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002 wortmannin), Src (PP2). Levels phosphorylated Akt, effector...
In the mammalian central nervous system glutamate is major excitatory neurotransmitter and plays a crucial role in plasticity toxicity of certain neural cells. We found that stimulated activation p38 stress-activated protein kinase (SAPK, also known as c-Jun N-terminal (JNK)), two subgroup members mitogen-activated superfamily matured cerebellar granule The was largely mediated by <i>N</i>-methyl-d-aspartate receptors. Furthermore, we have revealed novel signaling pathway, is,...
Abstract β‐Amyloid (Aβ), a major constituent of senile plaques in Alzheimer's disease (AD), is thought to contribute the neurodegeneration. We examined effects nicotinic receptor agonists on Aβ cytotoxicity cultured rat cortical neurons. The number viable neurons decreased significantly when cultures were exposed synthetic peptides (25–35). Concomitant administration nicotine with markedly reduced dead cells. This nicotine‐induced neuroprotection was dependent concentration. When...
Alzheimer's disease (AD) is characterized by the accumulation of fibrillar amyloid-beta (Abeta) peptides to form amyloid plaques. Understanding balance production and clearance Abeta key elucidating plaque homeostasis. Microglia in brain, associated with senile plaques, are likely play a major role maintaining this balance. Here, we show that heat-shock proteins (HSPs), such as HSP90, HSP70, HSP32, induce interleukin 6 tumor necrosis factor alpha increase phagocytosis peptides. This suggests...
Oxidative modification of cytoplasmic RNA in vulnerable neurons is an important, well documented feature the pathophysiology Alzheimer disease. Here we report that RNA-bound iron plays a pivotal role for oxidation disease brain. The cytoplasm hippocampal showed significantly higher redox activity and iron(II) staining than age-matched controls. Notably, both were susceptible to RNase, suggesting physical association with RNA. Ultrastructural analysis further suggested endoplasmic reticulum...
Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and oligodendrocytes in response to intrinsic extrinsic changes. Notch signals maintain undifferentiated NPCs, but the mechanisms underlying neuronal differentiation are largely unknown. We show that SIRT1, an NAD(+)-dependent histone deacetylase, modulates differentiation. SIRT1 was found cytoplasm of embryonic adult NPCs transiently localized nucleus stimulus. started translocate within 10 min after transfer conditions,...
Abstract: Nicotinic and muscarinic cholinergic receptors were studied in autopsied brains from four histologically normal controls five histopathologically verified cases of Alzheimer‐type dementia (ATD), using ligand binding techniques. assessed by (–)‐[ 3 H]nicotine [ H]quinuclidinyl benzilate ([ H]QNB), respectively. Compared with the controls, sites ATD brain regions examined significantly reduced putamen nucleus basalis Meynert (NbM). H]QNB was hippocampus NbM. These findings suggest...
It has been shown that estrogen replacement in menopausal women is effective slowing down the progression of cognitive impairment Alzheimer's disease. Although recent studies have demonstrated neuroprotective effects estrogen, precise mechanism neuroprotection not elucidated. In present study, we show phosphatidylinositol 3-kinase (PI3-K) cascade involved stimulated by estrogen. Exposure to glutamate reduced viability rat primary cortical neurons. Pretreatment with 10 nM 17beta-estradiol...
Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily characterized by the degeneration of dopaminergic neurons in nigrostriatal pathway. Previous studies have demonstrated chronic systemic exposure Lewis rats to rotenone produced many features PD, and cerebral tauopathy was also detected case severe weight loss. The present study designed assess neurotoxicity after daily oral administration for 28 days at several doses C57BL/6 mice. In addition, we examined...
Abstract Oxidative stress, a process in which neurotoxic oxygen free radicals cause dopaminergic neuronal degeneration, has been implicated the degenerative Parkinson's disease. Glutamate‐induced neurotoxicity is model of oxidative stress. We demonstrated that preincubation with D2‐type dopamine agonists bromocriptine and quinpirole provides neuroprotection against glutamate‐induced cultured rat mesencephalic neurons. Simultaneous administration D2 agonists, however, did not provide...
Decreased levels of protein kinase C (PKC) and a reduction in the vitro phosphorylation Mr 86,000 (P86), major PKC substrate, are biochemical characteristics brain tissue from patients with Alzheimer's disease (AD) (Cole et al., 1988). In current study, we utilized antibodies against individual isozymes to assess degree involvement different isoforms AD. The concentration PKC(beta II) was lower particulate fractions prepared AD hippocampal cortical than controls higher cytosol cortex...
Reduction of brain amyloid-β (Aβ) has been proposed as a therapeutic target for Alzheimer disease (AD), and microglial Aβ phagocytosis is noted an clearance system in brains. Galantamine acetylcholinesterase inhibitor approved symptomatic treatment AD. also acts allosterically potentiating ligand (APL) nicotinic acetylcholine receptors (nAChRs). APL-binding site located close to but distinct from that on nAChRs, FK1 antibody specifically binds the without interfering with...