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Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan Serneels Julie D.De Schutter Lies De Groef Lieve Moons Steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of biology University of PisaPisaItaly Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： Melissa A.Rudy Trent A.Watkins division of Neuroimmunology and Glial biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system ***,this stress response drives neuronal apoptosis in non-regenerative *** duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative *** dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve *** this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

Knockdown of Na,K-ATPase β-subunits in Oncopeltus fasciatus induces molting problems and alterations in tracheal morphology

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Insect Science 2023年第2期30卷 375-397页

作者： Marlena Herbertz Jennifer Lohr Christian Lohr Susanne Dobler division of Molecular Evolutionary biology Department of BiologyInstitute of Cell and Systems Biology of AnimalsUniversitat HamburgHamburg20146Germany division of Neurophysiology Department of BiologyInstitute of Cell and Systems Biology of AnimalsUniversitat HamburgHamburg20146Germany

The ubiquitously expressed transmembrane enzyme Na,K-ATPase(NKA)is vital in maintaining functionality of *** association of α-and β-subunits is believed to be essential for forming a functional *** the large milkweed bug Oncopeltus fasciatus fourα1-paralogs and four β-subunits exist that can associate into NKA *** diversity raises the question of possible tissue-specific distribution and *** the α1-subunits are known to modulate cardenolide-resistance and ion-transport efficiency,the functional importance of the β-subunits needed further *** here characterize all four different β-subunits at the cellular,tissue,and whole organismal scales.A knockdown of different β-subunits heavily interferes with molting success resulting in strongly hampered *** failure of ecdysis might be related to disrupted septate junction(SJ)formation,also reflected in β2-suppression-induced alteration in tracheal *** data further suggest the existence of isolated β-subunits forming homomeric or β-heteromeric *** possible standalone and structure-specific distribution of the β-subunits predicts further,yet unknown pump-independent *** different effects caused byβknockdowns highlight the importance of the various β-subunits to fulfill tissue-specific requirements.

关键词： ecdysis insect Na^(+)/K^(+)-ATPase protein distribution RNAi septate junctions tissue-specific function

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Potential of kynurenine metabolites in drug development against neurodegenerative diseases

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Neural Regeneration Research 2021年第2期16卷 308-309页

作者： Lenka Kubicova Vladimir Chobot division of Molecular systems biology Department of Ecogenomics and Systems BiologyFaculty of Life SciencesUniversity of ViennaViennaAustria

Reactive oxygen species(ROS)and kynurenines:Kynurenines represent a relatively heterogenous group of tryptophan metabolites(Figure 1 A).The amino acid tryptophan is metabolized in the humans by the kynurenine or serotonin *** a long time,the kynurenine pathway was assumed primarily to constitute the source for nicotinamide-adenine dinucleotide phosphate,one of the most utilized redox active enzyme cofactors.

关键词： Figure assumed utilized

A multilevel pan-cancer map links gene mutations to cancer hallmarks

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Chinese Journal of Cancer 2015年第10期34卷 439-449页

作者： Theo A.Knijnenburg Tycho Bismeijer Lodewyk F.A.Wessels llya Shmulevich Institute for systems biology Bioinformatics and Statistics Division of Molecular CarcinogenesisNetherlands Cancer Institute

Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are *** study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics ***:We created a map that connects genes to cancer hallmarks via signaling *** projected gene mutation and focal copy number data from various cancer types onto this *** performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this ***:Our analysis showed that although the genetic fingerprint of tumor types could be very different,there were less variations at the level of hallmarks,consistent with the idea that different genetic alterations have similar functional ***,we showed how the multilevel map could help to clarify the role of infrequently mutated genes,and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways,whereas many co-occurring gene mutations were associated with hallmark ***:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks.

关键词： Cancer systems biology, Cancer hallmarks, Gene mutations, Multilevel model

Strategies to increase tolerance and robustness of industrial microorganisms

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Synthetic and systems Biotechnology 2022年第1期7卷 533-540页

作者： Marta Tous Mohedano Oliver Konzock Yun Chen division of systems and Synthetic biology Department of Biology and Biological EngineeringChalmers University of TechnologyGöteborgSweden

The development of a cost-competitive bioprocess requires that the cell factory converts the feedstock into the product of interest at high rates and ***,microbial cell factories are exposed to a variety of different stresses during the fermentation *** stresses can be derived from feedstocks,metabolism,or industrial production processes,limiting production capacity and diminishing *** stress tolerance and robustness allows for more efficient production and ultimately makes a process more economically *** review summarises general trends and updates the most recent developments in technologies to improve the stress tolerance of *** first look at evolutionary,systems biology and computational methods as examples of non-rational *** we review the(semi-)rational approaches of membrane and tran-scription factor engineering for improving tolerance *** further discuss challenges and perspectives associated with these different approaches.

关键词： Toxicity Novel synthetic biology tools systems biology Genome-scale model Membrane engineering Transcription factor engineering

Asymmetrical free diffusion with orientation-dependence of molecules in finite timescales

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Science China(Physics,Mechanics & Astronomy) 2013年第6期56卷 1047-1052页

作者： SHENG Nan TU YuSong GUO Pan WAN RongZheng FANG HaiPing division of Interfacial Water Shanghai Institute of Applied Physics Chinese Academy of Sciences Institute of systems biology Shanghai University

Using molecular dynamics simulations, we show that free diffusion of a nanoscale particle (molecule) with asymmetric structure critically depends on the orientation in a finite timescale of picoseconds to nanoseconds. In a timescale of ~100 ps, there are ~10% more possibilities for the particle moving along the initial orientation than moving opposite to the orientation; and the diffusion distances of the particle reach ~1 nm. We find that the key to this observation is the orientation-dependence of the damping force to the moving of the nanoscale particle and a finite time is required to regulate the particle orientation. This finding extends the work of Einstein to nano-world beyond random Brownian motion, thus will have a critical role in the understanding of the nanoscale world.

关键词： orientation diffusion finite timescales