A5046413444- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- Botulinum Toxin and Related Neurological Disorders
- Cellular transport and secretion
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Amyotrophic Lateral Sclerosis Research
- Ginkgo biloba and Cashew Applications
- Autism Spectrum Disorder Research
- Nerve injury and regeneration
- Virus-based gene therapy research
- Multiple Sclerosis Research Studies
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Folate and B Vitamins Research
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
Osaka University
2015-2024
Universiti Tunku Abdul Rahman
2011-2012
Significance Lewy bodies (LBs), which mainly consist of α-syn, are neuropathological hallmarks patients with Parkinson’s disease (PD). Recently, it has been reported that aggregates α-syn cross-β structures capable propagating within the brain in a prionlike manner. However, there is still no evidence such propagation occurs patient’s brain. Here, we examined LBs thin sections autopsy brains PD using microbeam X-ray diffraction (XRD) and confirmed structure exist patients. Our finding...
Abstract Parkinson’s disease (PD) is a neurodegenerative caused by the loss of dopaminergic neurons in substantia nigra. A characteristic pathological feature PD cytoplasmic accumulation α-synuclein (SNCA) protein. Multiplication SNCA gene familial and protein during progression sporadic suggest that increased levels increase risk PD. Thus, reducing expression could delay onset or modify course. For efficient knock down, we designed synthesized an amido-bridged nucleic acids (AmNA)-modified...
Mitochondrial quality control, which is crucial for maintaining cellular homeostasis, has been considered to be achieved exclusively through mitophagy. Here we report an alternative mitochondrial control pathway mediated by extracellular mitochondria release. By performing time-lapse confocal imaging on a stable cell line with fluorescent-labeled mitochondria, observed release of from cells into the space. Correlative light-electron microscopy revealed that majority are in free form and,...
Abstract Lewy bodies (LBs), which mainly consist of α-synuclein (α-syn), are neuropathological hallmarks patients with Parkinson’s disease (PD). The fine structure LBs is unknown and cannot be made artificially. Nevertheless, many studies have described fibrillisation using recombinant α-syn purified from E. coli . An extremely fundamental problem whether the same as that amyloid fibrils. Thus, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to analyse in brain PD...
The neuron-to-neuron propagation of misfolded α-synuclein (αSyn) aggregates is thought to be key the pathogenesis synucleinopathies. Recent studies have shown that extracellular αSyn taken up by endosomal–lysosomal system can rupture lysosomal vesicular membrane; however, it remains unclear whether leads transmission aggregation. Here, we applied cell-based models show ruptured lysosomes are pathway through which exogenous transmit aggregation, and furthermore, this process was prevented...
Abstract Parkinson’s disease is a neurodegenerative characterized by the formation of neuronal inclusions α-synuclein in patient brains. As progresses, toxic aggregates transmit throughout nervous system. No effective disease-modifying therapy has been established, and preventing aggregation thought to be one most promising approaches ameliorate disease. In this study, we performed two-step screening using thioflavin T assay cell-based identify inhibitors. The first screening, assay, allowed...
Abstract The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes evaluate how much dysregulation is associated levodopa dose. Furthermore, effect of Opicapone, a catechol‐ o ‐methyl‐transferase inhibitor, on by monitoring AST ALT treated Levodopa–Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum were measured (PD, n = 72 controls, 31). level was compared total dose, clinical parameters, blood...
Abstract Lipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson’s disease (PD). However, it not fully determined which lipids are involved initiation αSyn aggregation PD. Here exploiting genetic understanding associating loss-of-function mutation Synaptojanin 1 (SYNJ1), a phosphoinositide phosphatase, familial PD and analysis postmortem brains, we identified novel lipid molecule toxic conversion its relation to We first established SYNJ1 knockout...
α-Synucleinopathies are a subgroup of neurodegenerative diseases including dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Pathologically, these disorders can be characterized by the presence intraneuronal aggregates composed mainly α-synuclein (αSyn), which called neurites. Recent report showed that more than 90% αSyn present in form very small deposits presynaptic terminals affected neurons DLB. However, mechanisms responsible for accumulation abnormal remain unclear. In this...
ABSTRACT Objective Alpha‐synuclein (α‐syn) is a major component of Lewy bodies, which are the pathological hallmark in Parkinson's disease, and its genetic mutations cause familial forms disease. Patients with α‐syn G51D mutation exhibit severe clinical symptoms. However, vitro studies showed low propensity for mutation. We studied mechanisms associated neurotoxicity using murine model generated by fibril injection into brain. Methods Structural analysis wild‐type α‐syn‐fibrils were...
Abstract We previously synthesized new 5-thienyl-substituted 2-aminobenzamide-type HDAC1, 2 inhibitors with the (4-ethyl-2,3-dioxopiperazine-1-carboxamido) methyl group. K-560 ( 1a ) protected against neuronal cell death in a Parkinson’s disease model by up-regulating expression of XIAP. This finding prompted us to design K-560-related compounds. examined structure activity relationship (SAR) for protective effects newly and known derivatives after cerebral ischemia. Among them, K-856 8 ),...
Accumulating evidence has shown that the inflammatory process participates in pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential anti-inflammatory agents. Janus kinase 2 (JAK2), one key molecules inflammation, transduces signals downstream various cytokines, and some inhibitors have already been clinically applied to treatment diseases. However, efficacy JAK2 ALS remains be demonstrated. In this study, we examined role by administering selective...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by several pathologies including oxidative stress, apoptosis, neuroinflammation, and glutamate toxicity. Although multiple reports suggest that ischemia hypoxia in the spinal cord plays pivotal role pathogenesis of ALS, precise progression remains unknown. In this study, we detected higher expression levels Hypoxia-inducible factor 1-alpha (HIF-1α), key regulator cellular responses to hypoxia, ALS...