A5018411675- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neural Engineering
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Microbial Community Ecology and Physiology
- Botulinum Toxin and Related Neurological Disorders
- Marine Toxins and Detection Methods
- Mesenchymal stem cell research
- Genetic Neurodegenerative Diseases
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- Periodontal Regeneration and Treatments
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- Inflammatory mediators and NSAID effects
- Advanced Memory and Neural Computing
- Receptor Mechanisms and Signaling
- Cholesterol and Lipid Metabolism
Johns Hopkins Medicine
2016-2023
Johns Hopkins University
2016-2023
Orthopaedic Research Foundation
2022-2023
Stomatology Hospital
2017
Peking University
2004-2017
The University of Tokyo
2011-2014
INTRODUCTION Parkinson’s disease (PD) is the second most common neurodegenerative disorder and leads to slowness of movement, tremor, rigidity, and, in later stages PD, cognitive impairment. Pathologically, PD characterized by accumulation α-synuclein Lewy bodies neurites. There degeneration neurons throughout nervous system, with dopamine substantia nigra pars compacta leading major symptoms PD. RATIONALE In brains patients, pathologic seems spread from cell via self-amplification,...
Significance Recent studies have identified a helically folded tetramer as the major normal structure of α-synuclein (α-syn) and that resists aggregation. However, underlying mechanisms regulate formation α-syn tetramers remain elusive. Our study shows mutations in glucocerebrosidase 1 ( GBA1 ) depletion-induced deficiency leading to accumulation glycosphingolipids (GSLs) are sufficient cause destabilization increase susceptibility human dopaminergic neurons cytotoxicity due exposure...
A method to culture human cortical neurons that yielded a balanced network of excitatory and inhibitory revealed these cells die in PARP-dependent manner after neurotoxic insult.
Pathologic α-synuclein plays an important role in the pathogenesis of α-synucleinopathies such as Parkinson’s disease (PD). Disruption proteostasis is thought to be central pathologic toxicity; however, molecular mechanism this deregulation poorly understood. Complementary proteomic approaches cellular and animal models PD were used identify characterize interactome. We report that highest biological processes interacted with mice included RNA processing translation initiation. Regulation...
Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2+ /calmodulin-dependent protein kinase phosphorylates the tail domain KIF17, a member kinesin superfamily, control subunit 2B (GluN2B) transport by changing KIF17–cargo interaction in vitro . However, mechanisms regulation GluN2B vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 ( TgS ), or with S1029A TgA ) S1029D TgD phosphomimic mutations...
Shewanella algae, which produces tetrodotoxin and exists in various seafoods, can cause human diseases, such as spondylodiscitis bloody diarrhea. In the present study, we focused on temporal, dynamic process salt-stressed S. algae by monitoring gene transcript levels at different time points after high salt exposure. Transcript changes amino acid metabolism, carbohydrate energy membrane transport, regulatory functions, cellular signaling were found to be important for response algae. The...
The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing exons ATAD1, gene encoding Thorase, cohort patients with schizophrenia and healthy controls revealed rare variants. These variants caused defects glutamatergic signaling impairing AMPAR internalization recycling mouse primary cortical neurons. This...
The human cerebral cortex is a complex structure with tightly interconnected excitatory and inhibitory neuronal networks. In order to study cortical function, we recently developed method generate neurons from induced pluripotent stem cells (hiPSCs) that form both networks resembling the composition of cortex. These cultures organoids recapitulate populations representative six layers balanced network functional homeostatically stable. To determine whether hiPSC-derived can integrate retain...
The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization AMPARs from synaptic membrane. Here, we show N-methyl-d-aspartate (NMDAR) activation leads to increased S-nitrosylation N-ethylmaleimide-sensitive factor (NSF). stabilizes Thorase-AMPAR complexes enhances AMPAR interaction with protein-interacting...
Interspecies chimeras offer great potential for regenerative medicine and the creation of human disease models. Whether pluripotent stem cell–derived neurons in an interspecies chimera can differentiate into functional integrate host neural circuity is not known. Here, we show, using Engrailed 1 (En1) as a development niche, that naive-like embryonic cells (ESCs) incorporate adult mouse brains. Human-derived including tyrosine hydroxylase (TH)+ brain at low efficiency. These TH+ have...
Calcium regulation is a critical process in neurons, and Ca2+ signaling major contributor to neurological disorders including Parkinson's disease (PD). Here, combining calcium imaging with whole-cell current recording, we provide detailed protocol for measuring homeostasis dopaminergic (DA) neurons derived from human induced pluripotent stem cells (hiPSCs). This approach can be applied investigate the role of neuronal functionality as well processes. For complete details on use execution...
The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) causes familial Parkinson’s disease (PD) and is also found a subset of idiopathic cases. Prior studies Drosophila human induced pluripotent stem cell (iPSC)-derived dopamine neurons uncovered pronounced effect LRRK2 on mRNA translation. It was previously reported that promotes translation mRNAs with complex 5′ untranslated region (UTR) secondary structure, resulting increased expression calcium channels dysregulated homeostasis...
Human neuron transplantation offers novel opportunities for modeling human neurologic diseases and potentially replacement therapies. However, the complex structure of cerebral cortex, which is organized in six layers with tightly interconnected excitatory inhibitory neuronal networks, presents significant challenges vivo techniques to obtain a balanced, functional homeostatically stable network. Here, we present protocol introduce induced pluripotent stem cell (hiPSC)-derived neural...
Pathologic α-syn destabilizes the TSC 1 and 2 complex leading to mTORC1 activation, enhanced protein translation neurodegeneration in PD. Abstract: Pathological α-synuclein (α-syn) plays an important role pathogenesis of α-synucleinopathies such as Parkinson’s disease (PD). Disruption homeostasis is thought be central PD pathogenesis, however molecular mechanism this deregulation poorly understood. Here we report that pathologic binds tuberous sclerosis (TSC) TSC1-TSC2 activation mechanistic...