A5053778844- Ubiquitin and proteasome pathways
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Muscle Physiology and Disorders
- Neurological Disease Mechanisms and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Genetics and Neurodevelopmental Disorders
- Dementia and Cognitive Impairment Research
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- Connective tissue disorders research
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Renal Diseases and Glomerulopathies
- Galectins and Cancer Biology
- Medical Imaging and Pathology Studies
- Health, Environment, Cognitive Aging
- Cardiac tumors and thrombi
- Bacterial Infections and Vaccines
- S100 Proteins and Annexins
- Histone Deacetylase Inhibitors Research
- Renal cell carcinoma treatment
- Genetic and Kidney Cyst Diseases
- Cholinesterase and Neurodegenerative Diseases
Kyoto University
2010-2024
National Center for Geriatrics and Gerontology
2018-2021
Hospital for Sick Children
1997
Kitano Hospital
1990
Evidence suggests that protein misfolding is crucially involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, controversy still exists regarding involvement proteasomes or autophagy ALS due to previous conflicting results. Here, we show impairment ubiquitin-proteasome system, but not autophagy-lysosome system motor neurons replicates mice. Conditional knock-out mice proteasome subunit Rpt3 a neuron-specific manner (Rpt3-CKO) showed locomotor dysfunction accompanied by...
Adult muscle stem cells (satellite cells) are required for adult skeletal regeneration. A proper balance between quiescence, proliferation, and differentiation is essential the maintenance of satellite cell pool their regenerative function. Although ubiquitin-proteasome most protein degradation in mammalian cells, how its dysfunction affects tissue remains unclear. Here, we investigated function proteasome using mice lacking crucial proteasomal component, Rpt3. Ablation Rpt3 decreased...
The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein organelle clearance. role proteasome pathway in mammalian muscle has not been examined vivo. In this study, we report that muscle-specific deletion a crucial proteasomal gene, Rpt3 (also known as Psmc4), resulted profound growth defects decrease force production mice. Specifically, developing muscles conditional Rpt3-knockout animals showed dysregulated activity. autophagy was upregulated, but...
The deposition of Amyloid-beta peptides (Aβ) is detected at an earlier stage in Alzheimer's disease (AD) pathology. Thus, the approach toward Aβ metabolism considered to play a critical role onset and progression AD. Mounting evidence suggests that lifestyle-related diseases are closely associated with AD, exercise especially linked prevention delayed We previously showed more effective than diet control against pathology cognitive deficit AD mice fed high-fat diet; however, underlying...
Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We reported that a high fat diet (HFD) promotes amyloid precursor protein (APP) cleavage by β-site APP cleaving enzyme 1 (BACE1) without increasing BACE1 levels in transgenic mice. However, the detailed mechanism had remained unclear. Here we demonstrate HFD BACE1/Adaptor protein-2 (AP-2)/clathrin complex formation AP-2 In Swedish overexpressing Chinese hamster ovary (CHO) cells as well SH-SY5Y cells, overexpression...
Introduction Although diabetes and apolipoprotein E (apoE) are both significant risk factors for dementia, including Alzheimer's disease, it remains to be clarified how they related each other in contributing the of dementia. Methods By reviewing National Coordinating Center (NACC) clinical records, we investigated whether affects cognitive decline depending on APOE genotype their potential relationships with neuropathology. Results A interaction between exists, where affected APOE3 carriers...
Abstract Background Subcortical ischemic vascular dementia, one of the major subtypes is characterized by lacunar infarcts and white matter lesions caused chronic cerebral hypoperfusion. In this study, we used a mouse model bilateral common carotid artery stenosis (BCAS) to investigate role B-cell translocation gene 2 (BTG2), an antiproliferation gene, in glial response Methods Btg2 −/− mice littermate wild-type control underwent BCAS or sham operation. Behavior phenotypes were assessed...
Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) neurodegeneration. Although the mechanisms underlying these associations remain elusive, bidirectional interactions between obesity/diabetes may be involved in them. Both AD significantly reduce life expectancy. We generated AppNL-F/wt knock-in; ob/ob mice by crossing knock-in to investigate whether amyloid-β (Aβ) affects lifespan of mice. displayed shortest compared wild-type mice,...
Significance Statement The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal (APLS) are major intracellular protein degradation mechanisms. importance of APLS in podocytes is established, but role UPS not well understood. first mouse model podocyte-specific proteasome impairment revealed that plays important roles podocyte homeostasis, inducing p53-mediated apoptosis mTOR-mediated autophagy suppression. with impaired proteasomes exhibited characteristic features aging increase a...
✓ The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two calcium-binding proteins: parvalbumin (PV) calbindin D28K (CaBP). Hydrocephalus was induced 16 adult Wistar rats by intracisternal injection of a kaolin solution, which confirmed microscopically via atlantooccipital dural puncture. Four control received the same volume sterile saline. Immunohistochemical staining GAD, PV,...
The ubiquitin–proteasome system has the capacity to degrade polyubiquitinated proteins and plays an important role in many cellular processes. However, of Rpt3 depletion not been investigated adult muscles vivo. Herein, we generated skeletal-muscle-specific knockout mice, which genetic inactivation could be induced by doxycycline administration. Rpt3-knockout mice showed a significant reduction more than 90% expression Rpt3, crucial proteasomal gene, muscles. Using this model, found that...
Abstract Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, accumulations brains patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, introducing several ELISAs that target different epitopes, we accumulated postmortem depending on stage, brain areas, other AD-related changes. Notably, insoluble fraction determined each differ epitopes antibodies: non-AD control samples yield...
Abstract Protein turnover is crucial for cell survival, and the impairment of proteostasis leads to death. Aging associated with a decline in proteostasis, as progressive accumulation damaged proteins hallmark age-related disorders such neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that declining function ubiquitin-proteasome system (UPS) motor neurons contributes sporadic ALS pathologies, neuron loss, protein accumulation, glial...
Owing to recent advancements in imaging techniques and biomarker research, the natural history of Alzheimer's disease (AD) has become clear from very first preclinical stage. According study, more than 20 years before onset AD, Aβ starts accumulate brain. This induces neurofibrillary tangle formation cerebral isocortex, leading cognitive decline. If this process is suppressed, activity can be controlled. However, at point, best most realistic way deal with AD target environmental factors...