A5013397970- Muscle Physiology and Disorders
- Asthma and respiratory diseases
- Cardiomyopathy and Myosin Studies
- Amyotrophic Lateral Sclerosis Research
- Urticaria and Related Conditions
- Mast cells and histamine
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Myasthenia Gravis and Thymoma
- Cell death mechanisms and regulation
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Sirtuins and Resveratrol in Medicine
- Sphingolipid Metabolism and Signaling
- PARP inhibition in cancer therapy
- Lipid Membrane Structure and Behavior
- Electrodeposition and Electroless Coatings
- Neuroinflammation and Neurodegeneration Mechanisms
- Silk-based biomaterials and applications
- RNA modifications and cancer
- CAR-T cell therapy research
- Receptor Mechanisms and Signaling
- Copper Interconnects and Reliability
- Blood Coagulation and Thrombosis Mechanisms
Takeda (Japan)
2006-2025
Hokkaido University
2002-2005
The dysregulation of follicular helper T (Tfh) cell function, followed by the proliferation self-reactive B cells, can lead to development autoimmune diseases. Recently, adaptive regulatory (Treg) transfer therapy has attracted considerable attention for inducing effective immune tolerance owing Tregs' diverse immune-inhibitory activities. However, preclinical studies and recent clinical trials polyclonal Treg have suggested further improving efficacy through targeted tissue specificity...
A novel series of non-amidine-based C1s inhibitors have been explored. Starting from high-throughput screening hit 3, isoquinoline was replaced with 1-aminophthalazine to enhance inhibitory activity while exhibiting good selectivity against other serine proteases. We first disclose a crystal structure complex and small-molecule inhibitor (4e), which guided structure-based optimization around the S2 S3 sites further by over 300-fold. Improvement membrane permeability incorporation fluorine at...
Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%–15% of cases presents diagnostic challenges especially in early-onset female patients who often show disease resistance to immunosuppressive therapy. Furthermore, the immunopathology remains unclear. Thus, this study, we aimed elucidate pathogenic mechanism using scRNA-seq...
The Rpn10 subunit of the 26S proteasome can bind to polyubiquitinoylated and/or ubiquitin-like proteins via ubiquitin-interacting motifs (UIMs). Vertebrate consists five distinct spliced isoforms, but specific functions these variants remain largely unknown. We report here that one alternative products Xenopus Rpn10, named Xrpn10c, as a receptor for Scythe/BAG-6, which has been reported regulate Reaper-induced apoptosis. Deletional analyses revealed Scythe at least two domains responsible...
Recognition of polyubiquitinated substrates by the 26S proteasome is a key step in selective degradation various cellular proteins. The Rpn10 subunit can bind polyubiquitin conjugates vitro. We have previously reported unique diversity Rpn10, which differs from other multiple subunits, and that mouse mRNA family generated single gene developmentally regulated alternative splicing. To determine whether such splicing mechanisms occur species, we searched for isoforms databases our original PCR...
Duchenne muscular dystrophy is known to be caused by a defective gene of dystrophin, 427-kDa cytoskeletal protein, but the effective therapeutic drug presently unavailable. We previously reported that trypsin-like protease designated as dystrypsin markedly activated in muscle microsomal fraction immediately before onset clinical signs mdx mice, dystrophin-deficient hereditary animal model for human dystrophy. In order examine possible participation occurrence disease, we investigated effects...
<title>Abstract</title> The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral cells this context remains controversial. Here, we conducted single-cell RNA-sequencing blood mononuclear comprehensively profile concerning rate patients ALS. Our analysis revealed increased frequencies T helper 17 (Th17) relative regulatory cells, effector CD8 naïve and CD16highCD56low mature natural killer...
The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral cells this context remains controversial. Here, we conducted single-cell RNA-sequencing blood mononuclear comprehensively profile concerning rate patients ALS. Our analysis revealed increased frequencies T helper 17 (Th17) relative regulatory cells, effector CD8 naïve and CD16highCD56low mature natural killer CD16lowCD56high rapidly...