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Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

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Neural Regeneration Research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and Translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar *** neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain *** reprogramming is a promising strategy to convert glial scars to neural ***,previous studies have reported inconsistent *** this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target *** results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive ***,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain *** summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

Acquisition of functional neurons by direct conversion:Switching the developmental clock directly

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Journal of Genetics and Genomics 2019年第10期46卷 459-465页

作者： Shuangquan Chen Juan Zhang Dongming Zhang Jianwei Jiao Institute of Zoology Chinese Academy of SciencesBeijing100101China School of Pharmaceutical Sciences Tsinghua UniversityBeijing100084China University of Chinese Academy of Sciences Beijing100049China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong226001China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing100101China

Identifying approaches for treating neurodegeneration is a thorny task but is important for a growing number of *** have focused on discovering the underlying molecular mechanisms of reprogramming and optimizing the technologies for acquiring *** conversion is one of the most important processes for treating neurological *** neurons derived from direct conversion,which bypass the pluripotency stage,are more effective,more quickly obtained,and are safer than those produced via induced pluripotent stem cells(iPSCs).Based on iPSC strategies,scientists have derived methods to obtain functional neurons by direct conversion,such as neuron-related transcriptional factors,small ***,and epigenetic *** this review,we discuss the present strategies for direct conversion of somatic cells into functional neurons and the potentials of direct conversion for producing functional neurons and treating neurodeeeneration.

关键词： Direct conversion Fibroblasts induced neurons Neurodegeneration

Neural grafting for Parkinson's disease:challenges and prospects

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Neural Regeneration Research 2017年第3期12卷 389-392页

作者： Thomas B.Stoker Nicholas F.Blair Roger A.Barker John van Geest Center for Brain Repair Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK Wellcome Trust-Medical Research Council Stem Cell Institute University of CambridgeCambridgeUK

Parkinson＇s disease（PD） is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia *** motor disorder responds well to dopamine-replacement therapies,though these result in significant adverse effects due to non-physiological release of dopamine in the striatum,and off-target ***-based regenerative treatments offer a potential means for targeted replacement of dopamine,in a physiological *** neurons for cell-based therapies can be obtained from several *** ventral mesencephalon tissue contains dopaminergic neuron progenitors,and has been transplanted into the striatum of PD patients with good results in a number of ***,the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical *** pluripotent stem cells can be used to generate dopaminergic neurons for transplantation,providing a source of autologous tissue for *** approach means that challenges associated with allografts,such as the potential for immune rejection,can be ***,the associated cost and difficulty in producing a standardized product from different cell lines means that,at present,this approach is not commercially viable as a cell-based *** neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson＇s disease,with trials due to commence in the next few *** there are ethical considerations to take into account when using embryonic tissue,the possibility of producing a standardized,optimized cell product means that this approach can be both effective,and commercially viable.

关键词： Parkinson's disease neural grafting embryonic stem cells induced pluripotent stem cells induced neurons cell-based therapies

Human stem cell modeling of neuropsychiatric disorders:from polygenicity to convergence

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Medical Review 2023年第4期3卷 347-350页

作者： Jubao Duan Center for Psychiatric Genetics NorthShore University Health System Research InstituteEvanston 60201ILUSA Department of Psychiatry and Behavioral Neuroscience The University of ChicagoChicago 60637ILUSA

Neuropsychiatric disorders(NPD)are prevalent and devastating,posing an enormous socioeconomic burden to modern *** genetic studies of NPD have identified a plethora of common genetic risk variants with small effect sizes and rare risk variants of high *** exciting,there is a pressing need to translate these genetic discoveries into better understanding of disease biology and more tailored clinical *** induced pluripotent stem cell(hiPSC)-derived 2D and 3D neural cultures are becoming a promising cellular model for bridging the gap between genetic findings and disease biology for *** the accessibility of patient biospecimen to convert into stem cells and the power of genome editing technology to engineer disease risk variants,hiPSC model holds the promise to disentangle the disease polygenicity,model genetic interaction with environmental factors,and uncover convergent gene pathways that may be targeted for more tailored clinical intervention.

关键词： brain organoids genomics induced neurons induced pluripotent stem cell neuropsychiatric disorder