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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall Department of molecular biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim Department of biochemistry&molecular biology Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea Department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. in this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

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Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

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Neural Regeneration Research 2025年第9期20卷 2464-2479页

作者： Said Hashemolhosseini Lea Gessler institute of biochemistry Medical FacultyFriedrich-Alexander-University of Erlangen-NürnbergErlangenGermany

Skeletal muscles are essential for locomotion,posture,and metabolic *** understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle *** process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle *** contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular *** muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate *** of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction *** development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as *** regulators coordinate the diffe rentiation of myoblasts into mature muscle *** pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient *** ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal *** interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular *** molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling *** recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular *** fact,research in the last few years now suggests that these two signaling pathways are interconnected and

关键词： canonical Wnt"Wingless-related integration site"pathway beta-catenin(CTNNB1) Hippo pathway myogenesis myotube neuromuscular junction satellite cell skeletal muscle fiber transcriptional co-activator with PDZ-binding motif(TAZ) T-cell-specific transcription factor/lymphoid enhancer-binding factor(TCF/LEF) TEA domain family member(TEAD) transducin-like enhancer of split(TLE) yes-associated protein 1(YAP1)

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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó Joan Serrano-Marín Rafael Rivas-Santisteban Jaume Lillo molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Tangled but ordered human mitochondrial tRNA maturation

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Science China Life Sciences 2025年

作者： Shi-Ying Yao Xiao-Long Zhou Key Laboratory of RNA innovation Science and Engineering CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences

Mitochondria are cellular organelles that originate from an endosymbiotic bacterial ancestor and are primarily responsible for ATP generation via oxidative phosphorylation (OXPHOS). OXPHOS is conducted by five mitochondrial respiratory complexes in the inner mitochondrial membrane. Human mitochondria possess a distinct genome, a small, circular, doublestranded DNA (mtDNA) of 16,569 base pairs.

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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke Ye Xue Zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of biochemistry and molecular biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic Medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic Medical institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Epigenetics in the modern era of crop improvements

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Science China Life Sciences 2025年

作者： Yan Xue Xiaofeng Cao Xiangsong Chen Xian Deng Xingwang Deng Yong Ding Aiwu Dong Chengguo Duan Xiaofeng Fang Lei Gong Zhizhong Gong Xiaofeng Gu Chongsheng He Hang He Shengbo He Xinjian He Yan He Yuehui He Guifang Jia Danhua Jiang Jianjun Jiang Jinsheng Lai Zhaobo Lang Chenlong Li Qing Li Xingwang Li Bao Liu Bing Liu Xiao Luo Yijun Qi Weiqiang Qian Guodong Ren Qingxin Song Xianwei Song Zhixi Tian Jiawei Wang Yuan Wang Liang Wu Zhe Wu Rui Xia Jun Xiao Lin Xu Zhengyi Xu Wenhao Yan Hongchun Yang Jixian Zhai Yijing Zhang Yusheng Zhao Xuehua Zhong Daoxiu Zhou Ming Zhou Yue Zhou Bo Zhu Jiankang Zhu Qikun Liu College of Life Sciences Institute of Life Science and Green Development Hebei University Biotechnology Research institute Chinese Academy of Agricultural Sciences College of biology Hunan Key Laboratory of Plant Functional Genomics and Developmental Regulation Hunan Engineering and Technology Research Center of Hybrid Rapeseed Hunan University institute of Advanced Agricultural Sciences School of Advanced Agricultural Sciences Peking University State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural University National institute of Biological Sciences Key Laboratory of Seed innovation Institute of Genetics and Developmental Biology Chinese Academy of Sciences School of Advanced Agricultural Sciences Peking-Tsinghua Center for Life Sciences Peking University Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry and Molecular Engineering Peking University Key Laboratory of Seed innovation State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental Biology Chinese Academy of Sciences State Key Laboratory of Wheat improvement Peking University Institute of Advanced Agricultural Sciences Shandong Laboratory of Advanced Agricultural Sciences in Weifang State Key Laboratory of Crop Stress Adaptation and improvement School of Life Sciences Henan University State Key Laboratory of Maize Bio-breeding National Maize Improvement Center Department of Plant Genetics and Breeding China Agricultural University Frontiers Science Center for molecular Design Breeding China Agricultural University Center for Crop Functional Genomics and molecular Breeding China Agricultural University Sanya institute of China Agricultural University Hainan Yazhou Bay Seed Laboratory institute of Advan

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades,our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits. With recent technological advancements, epigenetic regulations at the single-cell level and at the large-scale population level are emerging as new focuses. This review offers an in-depth synthesis of the diverse epigenetic regulations, detailing the catalytic machinery and regulatory functions. it delves into the intricate interplay among various epigenetic elements and their collective influence on the modulation of crop traits. Furthermore, it examines recent breakthroughs in technologies for epigenetic modifications and their integration into strategies for crop improvement. The review underscores the transformative potential of epigenetic strategies in bolstering crop performance, advocating for the development of efficient tools to fully exploit the agricultural benefits of epigenetic insights.

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Saccharomyces cerevisiae in neuroscience:how unicellular organism helps to better understand prion protein?

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Neural Regeneration Research 2021年第3期16卷 489-495页

作者： Takao ishikawa Department of molecular biology Institute of BiochemistryFaculty of BiologyUniversity of WarsawWarsawPoland

The baker's yeast Saccharomyces(S.)cerevisiae is a single-celled eukaryotic model organism widely used in research on life *** a unicellular organism,*** has some evident limitations in application to ***,yeast prions are extensively studied and they are known to share some hallmarks with mammalian prion protein or other amyloidogenic proteins found in the pathogenesis of Alzheimer's,Parkinson's,or Huntington's ***,the yeast *** has been widely used for basic research on aggregation properties of proteins in cellulo and on their ***,a yeast-based study revealed that some regions of mammalian prion protein and amyloidβ1–42 are capable of induction and propagation of yeast *** is one of the examples showing that evolutionarily distant organisms share common mechanisms underlying the structural conversion of prion proteins making yeast cells a useful system for studying mammalian prion *** has also been used to design novel screening systems for anti-prion compounds from chemical *** assays are cheap in maintenance and safe for the researcher,making them a very good choice to perform preliminary screening before further characterization in systems engaging mammalian cells infected with *** this review,not only classical red/white colony assay but also yeast-based screening assays developed during last year are *** analysis and research carried out using yeast prions force us to expect that prions are widely present in ***,the last few years brought us several examples indicating that the mammalian prion protein is no more peculiar protein–it seems that a better understanding of prion proteins nature-wide may aid us with the treatment of prion diseases and other amyloid-related medical conditions.

关键词： amyloid artificial prion baker's yeast budding yeast drug screening fusion protein neurodegenerative diseases prion protein yeast-based assay

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TRANSFORMiNG GENES iN DUCK HEPATiC CARCiNOMA——mht(raf) AND Ha-ras

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Science China Chemistry 1988年第11期31卷 1325-1332页

作者：谈红刘超亭洪伟娜汤国英张素胤陆志祥陈渊卿蒋惠秋顾健人 Shanghai Cancer institute Department of biochemistry & molecular biology

The transfection of NiH 3T3 cells was performed with DNAs from 2 duck primary hepatic carcinomas (DHC 40K, 9K) and i tumor-adjacent liver tissue (TAL, 9N). Transfectants were found from 40K, 9K and 9N DNAs. The secondary transfectants were obtained after transfection of RAT-1 cells with DNAs from primary transfectants. After hybridization with Ha-ras, Ki-ras, N-ras and mht oncogenes, it was found that duck mht (5.2 and 3.2 kb EcoRi fragments) and duck Ha-ras (3.4 kb EcoRi fragments) were present in all these *** is the first report on transforming genes in duck primary hepatic cancer as well as tumoradjacent liver tissue

关键词： duck liver eancer transfectiou Southern blot.

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EXPRESSiON OF N-ras GENE iN HUMAN PRiMARY HEPATOCARCiNOMA

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Science in China,Ser.B 1986年第2期29卷 181-186页

作者：胡利富王露萍居丽雯黄乐泓李晓林李秀珍顾健人 Department of biochemistry and molecular biology Shanghai Cancer institute

Poly(A)~+ RNA was isolated from 9 specimens of human primary hepatic carcinoma, 1 non-tumorous liver tissue adjacent to cancer and 1 normal liver tissue samples. The Oligo-dT cellulose-purified poly(A)~+ RNAs were subjected to formaldehyde agarose gel electrophoresis, Northern transfer and hybridization with various ancogene probes. Two RNA species, 5.6 kb and 2.2 kb wore identified by N-ras gone hybridization in 6 out of 9 mRNA samples from primary hepatic carcinoma specimen. N-ras specific mRNA was not detectable in mRNA samples from normal human liver and tumor surrounding cirrhotic tissue. No detectable hybridization of mRNA from hepatoma and normal liver with Ki-ras or Ha-ras was *** human N-ras gene has been identified in DNA of mouse transfeetants transformed with PHC DNA, it strongly suggests that N-ras gene might be responsible for the transforming activity of part of cases of human liver cancer.

关键词： PHC EXPRESSiON OF N-ras GENE iN HUMAN PRiMARY HEPATOCARCiNOMA RNA HCi

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