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Science China Chemistry 2025年第1期68卷 26-34页

作者： Yutao Zhang Juan Li Wei-Hong Zhu Zhiqian Guo Shanghai Key Laboratory of Functional Materials Chemistry Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology State Key Laboratory of Bioreactor Engineering Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell MetabolismEast China University of Science & Technology

Sequence-activated chemiluminescence(CL) technique offers a unique approach to detecting specific biomolecules or cellular events with high sensitivity and spatial resolution. The fundamental principle behind sequence-activated CL probes involves tailoring highly-controllable CL signals in response to specific sequences or events of interest, thus enabling high-contrast signals under complex physiological conditions. This sequential activation could be triggered by enzymes, reactive oxygen species(ROS), biothiols or changes in the microenvironment. These unique sequence-activated CL probes bestow several advantages, including minimal background, deep-tissue penetration, and the ability of non-invasive or minimally invasive detection. The sequence-activated CL techniques represent a significant advancement in molecular imaging and diagnostics. In this mini-review, we focus on the latest developments in sequential CL probes, addressing the technical challenges and discussing the future trajectory by harnessing CL signaling and molecular recognition.

关键词： chemiluminescnece sequence-activation in-vivo bioimaging cyclic peroxide

New aspects of a small GTPase RAB35 in brain development and function

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Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima Ken Sato Laboratory of molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João B.Relvas Institute of Research and Innovation in Health(i3S)and Institute for molecular and cell Biology(IBMC) University of PortoPortoPortugal Department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli Department of molecular and Translational Medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

A-kinase anchoring protein-mediated compartmentalization of pro-survival signaling in the retina

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Neural Regeneration Research 2025年第2期20卷 479-480页

作者： Joanna Mackiewicz Tomasz Boczek Department of molecular Neurochemistry Medical University of LodzLodzPoland

The retina plays a fundamental role in the process of vision,serving as the primary interface between external visual stimuli and the central nervous *** the retina is exposed to a variety of environmental stresses and deleterious insults,it is susceptible to a spectrum of pathological conditions that can detrimentally affect *** often leads to irreversible vision loss due to the injury of specific cell *** instance,inherited retinal degeneration and age-related macular degeneration can lead to the death of photoreceptors,while conditions like glaucoma and optic nerve injury can result in the loss of ganglion *** precise pathological mechanisms driving retinal degeneration remain largely elusive,although research utilizing mouse models suggests that disruptions in intracellular signal transduction pathways may play a pivotal *** pathways within the retina orchestrate various aspects of retinal physiology,including phototransduction,synaptic transmission,and neuronal survival.

关键词： degeneration utilizing irreversible

The actin-bundling protein Fascin-1 modulates ciliary signalling

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Journal of molecular cell Biology 2023年第4期15卷 1-16页

作者： Lena Brücker Stefanie Kornelia Becker Vanessa Maissl Gregory Harms Maddy Parsons Helen Louise May-Simera Cilia cell Biology Institute of Molecular PhysiologyJohannes Gutenberg University Mainz55128 MainzGermany Imaging Core Facility Cell Biology UnitUniversity Medical CentreJohannes Gutenberg University Mainz55101 MainzGermany randall centre for cell and molecular biophysics King's College LondonLondon SE11ULUK

Primary cilia are microtubule-based cell organelles important for cellular communication. Since they are involved in the regulation of numerous signalling pathways, defects in cilia development or function are associated with genetic disorders, collectively called ciliopathies. Besides their ciliary functions, recent research has shown that several ciliary proteins are involved in the coordination of the actin cytoskeleton. Although ciliary and actin phenotypes are related, the exact nature of their interconnection remains incompletely understood. Here, we show that the protein BBS6, associated with the ciliopathy Bardet–Biedl syndrome, cooperates with the actin-bundling protein Fascin-1 in regulating filopodia and ciliary signalling. We found that loss of Bbs6 affects filopodia length potentially via attenuated interaction with Fascin-1. Conversely, loss of Fascin-1 leads to a ciliary phenotype, subsequently affecting ciliary Wnt signalling, possibly in collaboration with BBS6. Our data shed light on how ciliary proteins are involved in actin regulations and provide new insight into the involvement of the actin regulator Fascin-1 in ciliogenesis and cilia-associated signalling. Advancing our knowledge of the complex regulations between primary cilia and actin dynamics is important to understand the pathogenic consequences of ciliopathies.

关键词： cilia actin Wnt signalling ciliopathy Bardet–Biedl syndrome filopodia

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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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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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

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research centre for molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

cGAS-STING: mechanisms and therapeutic opportunities

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Science China Life Sciences 2025年

作者： Mengyuan Zhang Changxin Wu Defen Lu Xing Wang Guijun Shang Shanxi Medical University School and Hospital of Stomatology Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials The Key Laboratory of Medical molecular cell Biology of Shanxi Province Institutes of Biomedical Sciences Shanxi University College of Life Sciences Shanxi Agricultural University

The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA(dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.

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