A5049975564- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- Cholinesterase and Neurodegenerative Diseases
- Immune cells in cancer
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Pharmacological Receptor Mechanisms and Effects
- Tryptophan and brain disorders
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
- Neurological diseases and metabolism
- Cerebral Palsy and Movement Disorders
- Advanced Neuroimaging Techniques and Applications
- biodegradable polymer synthesis and properties
- Nicotinic Acetylcholine Receptors Study
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Memory and Neural Mechanisms
- Hereditary Neurological Disorders
- RNA Research and Splicing
- Restless Legs Syndrome Research
- Neurological Disease Mechanisms and Treatments
Nagoya University
2014-2024
University of California, Los Angeles
2022
Tohoku University
2012-2015
RIKEN Center for Brain Science
2012-2015
National Center of Neurology and Psychiatry
2008
Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, morphology across the mouse central nervous system (CNS). We identified shared region-specific astrocytic genes functions explored cellular origins their regional diversity. gene networks correlated with morphology, several which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction candidate reduced morphological complexity...
A homozygous mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16). Sig1R localizes to mitochondria-associated membrane (MAM), which an interface mitochondria and endoplasmic reticulum. However, role MAM ALS not fully elucidated. Here, we identified p.L95fs as novel ALS16. ALS-linked variants were unstable incapable binding inositol 1,4,5-triphosphate type 3 (IP3R3). The onset mutant Cu/Zn superoxide dismutase (SOD1)-mediated...
Abstract Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer’s disease (AD). Although microglia aging and neurodegenerative model mice show a loss homeostatic phenotype activation disease-associated (DAM), correlation between those phenotypes degree neuronal cell not clarified. In this study, we performed RNA sequencing isolated from three representative mouse models, App NL - G F/NL F with amyloid pathology, rTg4510 tauopathy, SOD1 G93A motor neuron by...
Neuroinflammation, which includes both neuroprotective and neurotoxic reactions by activated glial cells infiltrated immune cells, is involved in the pathomechanism of amyotrophic lateral sclerosis (ALS). However, cytokines that regulate inflammatory response ALS are not clear. Here, we identify transforming growth factor-β1 (TGF-β1), upregulated astrocytes murine human ALS, as a negative regulator response. We demonstrate astrocyte-specific overproduction TGF-β1 SOD1G93A mice accelerates...
Abstract Neuroinflammation, which is characterized by activated microglia, astrocytes, infiltrating immune cells and the subsequent production of inflammatory mediators, linked to a pathological process common neurodegenerative diseases, such as Alzheimer's disease amyotrophic lateral sclerosis ( ALS ). Furthermore, increasing evidence suggests that glial surrounding motor neurons also contribute non‐cell autonomous neurodegeneration through neuroinflammation mediated these non‐neuronal...
Dominant mutations in superoxide dismutase 1 (SOD1) cause degeneration of motor neurons a subset inherited amyotrophic lateral sclerosis (ALS). The pathogenetic process mediated by misfolded and/or aggregated mutant SOD1 polypeptides is hypothesized to be suppressed protein refolding. This genetic study aimed test whether SOD1-mediated ALS pathology recapitulated mice could alleviated overexpressing longevity-related deacetylase SIRT1 whose substrates include transcription factor heat shock...
Increasing evidence implicates the role of cell types surrounding motor neurons, such as interneurons and glial cells, in non-cell autonomous neurodegeneration amyotrophic lateral sclerosis (ALS). C-boutons, large cholinergic synapses that innervate spinal α-motor neurons to control their excitability, are progressively lost from both human ALS mutant Cu/Zn superoxide dismutase 1 (SOD1)-ALS mice. Neuregulin-1 (NRG1), a trophic factor implicated neural development, transmission, synaptic...
There is compelling evidence that glial-immune interactions contribute to the progression of neurodegenerative diseases. The adaptive immune response has been implicated in disease processes amyotrophic lateral sclerosis (ALS), but it remains unknown if innate signaling also contributes ALS progression. Here we report deficiency adaptor TIR domain-containing inducing interferon-β (TRIF), which essential for certain Toll-like receptor (TLR) cascades, significantly shortens survival time and...
Abstract Abnormal accumulation of TAR DNA-binding protein 43 (TDP-43), a DNA/RNA binding protein, is pathological signature amyotrophic lateral sclerosis (ALS). Missense mutations in the TARDBP gene are also found inherited and sporadic ALS, indicating that dysfunction TDP-43 causative for ALS. To model TDP-43-linked ALS rodents, we generated knock-in mice with patient-derived M337V mutation. Homozygous developed normally without exhibiting detectable motor neurodegeneration. However,...
Abstract Misfolding of mutant Cu/Zn‐superoxide dismutase (SOD1) is a pathological hallmark in familial form amyotrophic lateral sclerosis. Pathogenic mutations have been proposed to monomerize SOD1 normally adopting homodimeric configuration and then trigger abnormal oligomerization proteins. Despite this, misfolded conformation leading the at physiological conditions still remains ambiguous. Here, we show that, around body temperature (∼37°C), maintains dimeric but lacks most its secondary...
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15–30 years before clinical diagnosis. Rodent models recapitulate aggressive Aβ and/or the pathology are essential for AD research. Accordingly, non-invasive early detection systems in these animal required to evaluate phenotypic changes, elucidate mechanism progression, facilitate development...
Alzheimer's disease (AD) is the most common form of dementia and characterized by accumulation amyloid β (Aβ) phosphorylated tau. Neuroinflammation, mainly mediated glial activation, plays an important role in AD progression. Although there growing evidence for anti-neuroinflammatory neuroprotective effects cannabinoid system modulation, detailed mechanism remains unclear. To address these issues, we analyzed expression levels receptor type II (Cnr2/Cb2) App
Intracellular mislocalization of TAR DNA-binding protein 43 (TDP-43), a nuclear DNA/RNA-binding involved in RNA metabolism, is pathological hallmark amyotrophic lateral sclerosis (ALS). Although the aggregation-prone, TDP-43 C-terminal domain widely considered as key component pathology ALS, recent studies including ours suggest that N-terminal fragments (TDP-∆C) may also contribute to motor dysfunction ALS. However, specific functions mice have not been elucidated. Here, we established...
Cystatin C (CysC) is a major protein component of Bunina bodies, which are pathological hallmark observed in the remaining motor neurons patients with amyotrophic lateral sclerosis (ALS). Dominant mutations SOD1 gene, encoding Cu/Zn superoxide dismutase (SOD1), causative for subset inherited ALS cases. Our previous study showed that CysC exerts neuroprotective effect against mutant SOD1-mediated toxicity vitro; however, vivo evidence beneficial effects mediated by remains obscure. Here we...
筋萎縮性側索硬化症(ALS)の病巣では,グリア細胞の活性化やT細胞の浸潤がおこり,様々な炎症関連因子が放出されるが,このような現象は「神経炎症」と呼ばれ,ALS病態への積極的な関与が示されている.ミクログリアでは神経栄養因子のみならず種々の神経傷害性因子が産生され,アストロサイトではグルタミン酸のクリアランスが低下するなどの機能的変化が生じ神経変性に関与すると考えられる.さらに著者らは,ミクログリアとT細胞による神経保護性の炎症反応を制御する因子としてアストロサイト由来のTGF-β1の重要性をみいだした.ALSにおける神経炎症の病態機序の解明を通じ,グリア細胞やT細胞を標的とした新たな治療法の開発が期待される.
We investigated 2 Japanese siblings with a complicated form of familial spastic paraplegia. Cranial magnetic resonance (MR) imaging revealed marked thinning the corpus callosum. Diffusion tensor (DTI) showed microstructural changes in thalamus, basal ganglia, and cerebral white matter, single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer very similar findings. DTI SPECT effectively global not by conventional MR imaging.
Abstract The evaluation of cranial nerves in magnetic resonance imaging ( MRI ) at early developmental stage has not been established amyotrophic lateral sclerosis ALS ). A 23‐year‐old man with familial developed peripheral facial nerve palsy, and showed the striking gadolinium enhancement on those an stage. His symptoms progressed rapidly he died approximately 3 months after onset. We identified a missense mutation exon 1 Cu/Zn superoxide dismutase gene SOD ‐1 ), resulting Cys6Gly (C6G)...