A5011727187- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Coenzyme Q10 studies and effects
- Cholinesterase and Neurodegenerative Diseases
- Adipose Tissue and Metabolism
- Folate and B Vitamins Research
- Protein Tyrosine Phosphatases
- T-cell and B-cell Immunology
- Computational Drug Discovery Methods
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Biochemical effects in animals
- Hemoglobin structure and function
- Diet and metabolism studies
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Ocular Surface and Contact Lens
- Epigenetics and DNA Methylation
- High Altitude and Hypoxia
- Retinal Development and Disorders
- Birth, Development, and Health
- Telomeres, Telomerase, and Senescence
- Cytokine Signaling Pathways and Interactions
Tokyo Metropolitan Institute of Gerontology
2006-2021
Institute of Aging
2009-2017
Juntendo University Hospital
2011-2017
University of Michigan
2016
Juntendo University
2005-2015
Shimizu (Japan)
2009
Tohoku University
2009
Iwate University
2009
Hirosaki University
2009
Nagase ChemteX (Japan)
2009
AbstractConstitutive autophagy is important for control of the quality proteins and organelles to maintain cell function. Damaged accumulate in aged organs. We have previously reported that cardiac-specific Atg5 (autophagy-related gene 5)-deficient mice, which was floxed out early embryogenesis, were born normally, showed normal cardiac function structure up 10 weeks old. In present study, determine longer-term consequences Atg5-deficiency heart, we monitored Atg5-deficient mice further 12...
Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely consequence degenerative process still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical age-related macular degeneration humans. Investigations senescent Sod1(-/-) different ages showed older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number drusen increased with age,...
Abstract Electrophilic compounds are a newly recognized class of redox‐active neuroprotective with electron deficient, electrophilic carbon centers that react specific cysteine residues on targeted proteins via thiol ( S ‐)alkylation. Although plants produce variety physiologically active compounds, the detailed mechanism action these remains unknown. Catechol ring‐containing have attracted attention because they become quinones upon oxidation, although not themselves electrophilic. In this...
Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed human aortic atherosclerotic lesion by Northern blot hybridization, as well situ hybridization. expression detected 24 out 25 samples aorta obtained from 17 autopsy cases, but not one normal sample....
The apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct sets integral proteins. Biosynthetic targeting proteins to the is mediated by cytosolic tail determinants, many which resemble signals involved in rapid endocytosis or lysosomal targeting. Since these are recognized adaptor proteins, we hypothesized that there could be epithelial‐specific adaptors sorting. Here, report identification a novel member medium chain family, named μ1B, closely related...
Cerebral amyloid angiopathy (CAA) due to beta-amyloid (Abeta) is one of the specific pathological features familial Alzheimer's disease. Abeta mainly consisting 40- and 42-mer peptides (Abeta40 Abeta42) exhibits neurotoxicity aggregative abilities. All variants Abeta40 Abeta42 found in CAA were synthesized a highly pure form examined for PC12 cells ability. mutants at positions 22 23 showed stronger than wild-type Abeta40. Similar tendency was observed whose 50-200 times that corresponding...
Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role development no direct evidence has been documented so far. In order to investigate significance heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive failure with specific molecular...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although understanding pathogenesis PD remains incomplete, increasing evidence from human and animal studies has suggested that oxidative stress an important mediator its pathogenesis. Astaxanthin (Asx), potent antioxidant, been thought to provide health benefits decreasing risk stress-related diseases. This study examined protective effects...
Abstract The aging process correlates with the accumulation of cellular and tissue damage caused by oxidative stress. Although previous studies have suggested that stress plays a pathologic role in development bone fragility, little direct evidence has been found. In order to investigate significance bones, we analyzed mice deficient cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, encoded Sod1 gene; Sod1−/−). this study, showed for first time vivo distinct weakness stiffness...
Abstract Mechanical stress and aging are major risk factors of cartilage degeneration. Human studies have previously reported that oxidative damage increased, while SOD2 protein was reciprocally downregulated in osteoarthritic degenerated cartilage. However, it remains unclear whether mitochondrial superoxide imbalance chondrocytes causes We herein demonstrate mechanical loading promoted generation selective Sod2 downregulation vivo inducer also expression vitro . A genetically manipulated...
Abstract Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to tissue. The number living osteocytes canalicular networks declines an age-dependent manner. However, pathological effects mitochondrial redox imbalances on metabolism have not been fully elucidated. We generated mice lacking superoxide dismutase 2 ( Sod2 ) osteocytes. Like aged bone, depletion positively enhanced production cellular vivo . A morphological analysis...
TRAF5 [tumor necrosis factor (TNF) receptor-associated 5] is implicated in NF-κB and c-Jun NH 2 -terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, lymphotoxin-β receptor. To investigate functional role vivo , we generated TRAF5-deficient mice gene targeting. Activation either or tumor factor, CD40 was not abrogated traf5 −/− mice. However, B cells showed defects proliferation up-regulation various surface...
Amyloid fibrils in Alzheimer's disease mainly consist of 40- and 42-mer β-amyloid peptides (Aβ40 Aβ42) that exhibit aggregative ability neurotoxicity. Although the aggregates Aβ are rich intermolecular β-sheet, precise secondary structure remains unclear. To identify amino acid residues involved β-sheet formation, 34 proline-substituted mutants Aβ42 were synthesized their neurotoxicity on PC12 cells examined. Prolines rarely present whereas they easily accommodated β-turn as a Pro-X corner....
Amyloid fibrils mainly consist of 40-mer and 42-mer peptides (Aβ40, Aβ42). Aβ42 is believed to play a crucial role in the pathogenesis Alzheimer's disease because its aggregative ability neurotoxicity are considerably greater than those Aβ40. The Aβ involving generation free radicals closely related S-oxidized radical cation Met-35. However, cation's origin mechanism stabilization remain unclear. Recently, structural models fibrillar Aβ40 based on systematic proline replacement have been...
produced from a larger precursor, termed amyloid precursor protein (APP).'The APP is receptor-like transmembrane protein, and the p located on region C
Protein L-isoaspartyl methyltransferase (PIMT) is suggested to play a role in the repair of aged protein spontaneously incorporated with isoaspartyl residues. We generated PIMT-deficient mice by targeted disruption PIMT gene elucidate biological vivo. died from progressive epileptic seizures grand mal and myoclonus between 4 12 weeks age. An anticonvulsive drug, dipropylacetic acid (DPA), improved their survival but failed cure fatal outcome. L-Isoaspartatate, putative substrate for PIMT,...