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7,159 results on '"Zhang, Zhijun"'

505. MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations.

Author

Biswas, Md Helal U, Almeida, Sandra, Lopez-Gonzalez, Rodrigo, Mao, Wenjie, Zhang, Zhijun, Karydas, Anna, Geschwind, Michael D, Biernat, Jacek, Mandelkow, Eva-Maria, Futai, Kensuke, Miller, Bruce L, and Gao, Fen-Biao

Subjects
Neurons, Humans, Extracellular Signal-Regulated MAP Kinases, tau Proteins, Cell Death, Cell Differentiation, Cell Survival, Gene Expression Regulation, Enzyme Activation, Mutation, Aged, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Induced Pluripotent Stem Cells, Frontotemporal Dementia, Cellular Reprogramming, Cellular Reprogramming Techniques, MMP-2, MMP-9, frontotemporal dementia, iPSCs, neuronal survival, neurons, tau, Dementia, Neurodegenerative, Stem Cell Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Neurosciences, Aging, Acquired Cognitive Impairment, Alzheimer's Disease, Rare Diseases, Brain Disorders, Genetics, 2.1 Biological and endogenous factors, Neurological, Biochemistry and Cell Biology, Clinical Sciences
Abstract

How mutations in the microtubule-associated protein tau (MAPT) gene cause frontotemporal dementia (FTD) remains poorly understood. We generated and characterized multiple induced pluripotent stem cell (iPSC) lines from patients with MAPT IVS10+16 and tau-A152T mutations and a control subject. In cortical neurons differentiated from these and other published iPSC lines, we found that MAPT mutations do not affect neuronal differentiation but increase the 4R/3R tau ratio. Patient neurons had significantly higher levels of MMP-9 and MMP-2 and were more sensitive to stress-induced cell death. Inhibitors of MMP-9/MMP-2 protected patient neurons from stress-induced cell death and recombinant MMP-9/MMP-2 were sufficient to decrease neuronal survival. In tau-A152T neurons, inhibition of the ERK pathway decreased MMP-9 expression. Moreover, ectopic expression of 4R but not 3R tau-A152T in HEK293 cells increased MMP-9 expression and ERK phosphorylation. These findings provide insights into the molecular pathogenesis of FTD and suggest a potential therapeutic target for FTD with MAPT mutations.

Published
2016

506. Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

Author

Silva, M Catarina, Cheng, Chialin, Mair, Waltraud, Almeida, Sandra, Fong, Helen, Biswas, M Helal U, Zhang, Zhijun, Huang, Yadong, Temple, Sally, Coppola, Giovanni, Geschwind, Daniel H, Karydas, Anna, Miller, Bruce L, Kosik, Kenneth S, Gao, Fen-Biao, Steen, Judith A, and Haggarty, Stephen J

Subjects
Biochemistry and Cell Biology, Biological Sciences, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Stem Cell Research - Induced Pluripotent Stem Cell - Human, Aging, Acquired Cognitive Impairment, Neurodegenerative, Dementia, Alzheimer's Disease, Rare Diseases, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research, Frontotemporal Dementia (FTD), 2.1 Biological and endogenous factors, Neurological, Amino Acid Substitution, Autophagy, Biomarkers, Cell Differentiation, Cell Line, Codon, Frontotemporal Dementia, Gene Expression Regulation, Humans, Induced Pluripotent Stem Cells, Mutation, Neural Stem Cells, Neurons, Protein Isoforms, Protein Processing, Post-Translational, Stress, Physiological, tau Proteins, Clinical Sciences, Biochemistry and cell biology
Abstract

Frontotemporal dementia (FTD) and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC)-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.

Published
2016

521. Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial

Author

Kong, Yan, primary, Zhou, Jiawei, additional, Zhao, Mingge, additional, Zhang, Yuhua, additional, Tan, Tingting, additional, Xu, Zhi, additional, Hou, Zhenghua, additional, Yuan, Yonggui, additional, Tan, Liangliang, additional, Song, Ruize, additional, Shi, Yachen, additional, Feng, Haixia, additional, Wu, Wei, additional, Zhao, Yang, additional, and Zhang, Zhijun, additional

Published
2023
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541. Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair

Author

Xu, Tongtong, Gan, Lin, Chen, Wei, Zheng, Dandan, Li, Hanlai, Deng, Shiyu, Qian, Dongliang, Gu, Tingting, Lian, Qianyuan, Shen, Gracie, An, Qingzhu, Li, Wanlu, Zhang, Zhijun, Yang, Guo-Yuan, Ruan, Huitong, Cui, Wenguo, and Tang, Yaohui

Abstract

The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system (CNS) injury. Maintaining brain immune homeostasis is crucial for restoring neurovascular function. In this study, an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit, thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery. This immunomodulatory crosstalk microsphere (MP/RIL4) was composed of microglia-targeted RAP12 peptide-modified interleukin-4 (IL-4) nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques. We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β, iNOS, and CD86, while upregulating levels of anti-inflammatory factors such as IL-10, Arg-1, and CD206 in microglia. In addition, injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke, promoted neurobehavioral recovery, and enhanced the crosstalk between immune cells and the neurovascular unit, thus increasing angiogenesis and neurogenesis of stroke mice. In summary, the immunomodulatory microspheres, capable of orchestrating the interaction between immune cells and neurovascular unit, hold considerable therapeutic potential for ischemic stroke and other CNS diseases.

Published
2025
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