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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular biology laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Multiple Signaling Pathways Control Tbx6 Expression during Xenopus Myogenesis

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 390-396页

作者： Pan-Feng FANG, Rui-Ying HU, Xing-Yue HE, and Xiao-Yan DING* laboratory of Molecular and cell biology, laboratory of Stem cell biology & Institute of Biochemistry and cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China laboratory of Molecular and cell biology Laboratory of Stem Cell Biology & Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200031 China

Tbx6 is critical for somite specification and myogenesis initiation. It has been shown that Activin/Nodal, VegT/Nodal, FGF, and BMP signaling pathways are involved early in specifying mesoderm or later in patterning mesoderm, and Xnot plays roles in setting up the boundary between notochord and paraxial mesoderm. In this study, we introduce the dominant negative form of above genes into embryos to evaluate if they are responsible for regulating Tbx6 expression. The results show that: (1) Activin/Nodal and VegT/Nodal signals are necessary for both initiation and maintenance of Tbx6 expression, and Nodal is sufficient to induce ectopic Tbx6 expression; (2) FGF signal is necessary for the initiation and maintenance of Tbx6, but it is not sufficient to induce Tbx6 expression; (3) BMP is also necessary for the expression of Tbx6, and the induction of Tbx6 expression by BMP is dose dependent; (4) Xnot has no effect on the expression of Tbx6. Our results suggest that several signaling pathways are involved in regulating Tbx6 expression, and pave the route to reveal the molecular mechanism of initiating myogenesis.

关键词： Tbx6 FGF BMP Activin/Nodal VegT/Nodal

Insights into female germ cell biology： from in vivo development to in vitro derivations

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Asian Journal of Andrology 2015年第3期17卷 415-420页

作者： Dajung Jung Kehkooi Kee Department of Basic Medical Sciences Center for Stem Cell Biology and Regenerative Medicine School of Medicine Tsinghua University Beijing 100084 China

Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments： namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

关键词： embryonic stem cell female germline stem cell folliculogenesis in vitro derivations meiotic initiation primordial germ cell

CYTOCHEMICAL STUDY OF ELECTRON MICROSCOPY ON FRUCTOSE 1,6-DIPHOSPHATASE AND URIDINE DIPHOSPHOGLUCOSE PYROPHOS PHORYLASE IN THE MESO PHYLL cellS OF Stevia rebaudiana BERTONI

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Science China Chemistry 1988年第2期31卷 171-178页

作者：李里(火昆),汪德耀 laboratory of cell biology Xiamen University laboratory of cell biology Xiamen University

The subcellular localizations of fructose 1,6-diphosphatase (FDPase, EC 3.***.3.11) and uridine diphos-phoglucose pyrophosphorylase (UDPG PPlase, UTP:α-D-glucose-I-phosphate uridylytransferase, EC 2.***.7.9) in the mesophyll cells of a new sweetener plant (Stevia rebaudiana Bertoni), both of which arecritical in carbohydrate metabolism, were determined and the activities of both enzymes in the leaves ofdifferent ages were compared in this study. This experiment reveals: FDPase is a membrane-bound enzymeand is specifically localized on the thylakoid membranes of chloroplasts and the plasmic *** is only found on the thylakoid membranes of chloroplasts in the young mesophyll cells, while it isfound on both the thylakoid membranes of chloroplasts and the plasmic membranes in the mature meso-phyll cells. UDPG PPlase is distributed in the cytoplasmic matrix freely, and is localized on Golgi flat-tened sacs and Colgi vesicles in a membrane-bound form. In this study, it is suggested that the chloropla

关键词： UDPG CYTOCHEMICAL STUDY OF ELECTRON MICROSCOPY ON FRUCTOSE 1,6-DIPHOSPHATASE AND URIDINE DIPHOSPHOGLUCOSE PYROPHOS PHORYLASE IN THE MESO PHYLL cellS OF Stevia rebaudiana BERTONI

Single-cell technologies: current and near future

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Science China Life Sciences 2025年第01期 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University National Key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Key laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of biology Medicine and HealthThe University of ManchesterManchesterUK Department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of Stem cell biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative Center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Department of Physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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Recombinant Mouse Canstatin Inhibits Chicken Embryo Chorioallantoic Membrane Angiogenesis and Endothelial cell Proliferation

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Acta Biochimica et Biophysica Sinica 2004年第12期36卷 845-850页

作者： Hou WH Wang TY Yuan BM Chai YR Jia YL Tian F Wang JM Xue LX laboratory for cell biology Zhengzhou University Zhengzhou 450052 China

Human canstatin, a 24 kD fragment of the alpha2 chain of type IV collagen, has been proved to be one of the most effective inhibitors of angiogenesis and tumor growth. To investigate in vivo antiangiogenesis activity and in vitro effects on endothelial cell proliferation of recombinant mouse canstatin, the cDNA of mouse canstatin was introduced into an expression vector pQE40 to construct a prokaryotic expression vector pQE-mCan. The recombinant mouse canstatin efficiently expressed in E. coli M15 after IPTG induction was monitored by SDS-PAGE and by Western blotting with an anti-hexahistidine tag antibody. The expressed mouse canstatin, mainly as inclusion bodies, accounted for approximately 35% of the total bacterial proteins. The inclusion bodies were washed, lysed and purified by the nickel affinity chromatography to a purity of approximately 93%. The refolded mouse canstatin was tested on the chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed. In addition, recombinant mouse canstatin potently inhibited endothelial cell proliferation with no inhibition on non-endothelial cells. Taken together, these findings demonstrate that the recombinant mouse canstatin effectively inhibited angiogenesis of the chicken embryo in a dose-dependent manner and specially suppressed in vitro the proliferation of human umbilical vein endothelial cells.

关键词： Angiogenesis Inhibitors Animals Blotting Western cell Proliferation Chick Embryo Chorioallantoic Membrane Collagen Type IV Endothelial cells Endothelium Vascular Humans Mice Molecular Sequence Data Neovascularization Physiologic Peptide Fragments Recombinant Proteins Research Support Non-U.S. Gov't

ORGANIZATION OF NUCLEOSKELETON AND ITS RELATION TO DNA TOPOLOGICAL ORGANIZATION

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Science China Chemistry 1989年第3期32卷 314-323,385-387页

作者：鲍仕登汪德耀 laboratory of cell biology Xiamen University

The organization of nucleoskeleton fibers and its relation to DNA organization in the interphase micronucleus of a ciliate (Stylonychia mytilus Muller) were investigated mainly by the macromolecular spreading procedure combined with electron microscopy. It was shown that the nucleoskeleton fibers are organized as a regular organization termed the nucleoskeleton subunit which is composed of a structural center and a number of branch-like fibers extending radiately from the center. The whole micronuclear skeletal network is composed of a number of the essential subunits which are connected with each other. The micronuclear DNA is closely associated with the nucleoskeleton subunit and constructed as highly ordered DNA loops which appear in some different forms of topological organization. After the DNA-rich nucleoskeleton is digested with proteinase K, the nucleoskeleton subunit disappears, while the DNA loses its regular organization and becomes very random and loose, which Suggests that the nucleoskeleton subunit plays very important roles in maintaining the topological organization of the iuterphase DNA. The nucleoskeleton subunit may be the essential organizational and functional unit of the interphase nucleoskeleton.

关键词： nucleoskeleton DNA loops micronucleus ciliate.

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Identification and Characterization of a Rat Novel Gene RSEP4 Expressed Specifically in Central Nervous System

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 501-507页

作者： Xi-Dao WANG1,2, Ling-Wei KONG1, Zhi-Qin XIE1, Yu-Qiu ZHANG3, Zhi-Xin LIN2, Zhi-Qi ZHAO3,Lei YU4, and Nai-He JING1* 1 laboratory of Molecular cell biology, laboratory of Stem cell biology, Institute of Biochemistry and cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China School of Life Science and Biotechnology, 2 Shanghai Jiaotong University, Shanghai 200030, China Institute of Neurobiology, Fudan University, Shanghai 200433, China 3 4 Department of cell biology, Neurobiology and Anatomy, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA laboratory of Molecular cell biology and Stem cell biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China

The low-abundantly expressed genes composed the majorities of the mRNAs expressed in the central nervous system (CNS), and were thought to be important for the normal brain functions. Through differential screening a low-abundance cDNA sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI) model, we have identified a novel rat gene, rat spinal-cord expression protein 4 gene (RSEP4). The total length of RSEP4 cDNA is 2006 bp, with a 501 nucleotide open reading frame (ORF) that encodes a 167 amino acid polypeptide. Northern blot revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization showed that the mRNA of RSEP4 was strongly expressed in the CA1, CA2, CA3 and DG regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory neurons of dorsal horn and large motor neurons of ventral horn of spinal cord. Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 293T cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These results suggest that RSEP4 may play some roles in the CNS.

关键词： central nervous system (CNS) rat Northern blot in situ hybridization