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Neural Regeneration Research 2025年第9期20卷 2581-2582页

作者： Marianne Bardy-Lagarde Narimène Asbelaoui Abdel Mouman Ghoumari umr1195 “Diseases and Hormones of the Nervous System”Inserm and University Paris-SaclayKremlin-BicêtreFrance

Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.

关键词： myelin CXCR4

Central role of altered phosphodiesterase 2-dependent signaling in the pathophysiology of cognition-based brain disorders

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Neural Regeneration Research 2025年第8期20卷 2302-2303页

作者： Asma Boulksibat Alessandra Tempio Barbara Bardoni Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR7275Inserm U1323ValbonneFrance

The second messengers 3',5'-cyclic adenosine monophosphate(cAMP)and 3',5'-cyclic guanosine monophosphate(cGMP)modulate molecular pathways that are involved in a large variety of cellular *** the brain,these processes include neurogenesis,neuronal differentiation,activation and function of microglia,and synaptic plasticity,finally resulting in memory formation.

关键词： formation processes finally

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

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Neural Regeneration Research 2025年第10期20卷 2938-2954页

作者： Danielle Fernezelian Philippe Rondeau Laura Gence Nicolas Diotel Universitéde La Réunion INSERMUMR 1188Diabète athérothrombose Thérapies Réunion Océan Indien(DéTROI)Saint PierreLa RéunionFrance

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these ***,the mechanisms by which these processes interact are not well *** this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound *** this end,we used zebrafish as a relevant model of neuroplasticity and brain repair ***,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days *** parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using *** found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were *** the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of ***,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial ***,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced *** conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this *** addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to

关键词： angiogenesis cerebral damage inflammation neurogenesis stab wound telencephalon vascular endothelial growth factor zebrafish

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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Neural Regeneration Research 2025年第5期20卷 1350-1363页

作者： Hui Li Laurent Seugnet Department of Neurology Xijing HospitalXi’anShaanxi ProvinceChina Centre de Recherche en Neurosciences de Lyon Integrated Physiology of the Brain Arousal Systems(WAKING)UniversitéClaude Bernard Lyon 1INSERM U1028CNRS UMR 5292BronFrance

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular *** the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other *** these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral *** the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of ***-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared *** their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy ***,they impact GABAergic neurons and the excitation/inhibition *** rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock *** mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully *** sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory *** mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these *** this context,the Drosophila model,though underutilized,holds promise in shedding new light on these *** findings indicate its po

关键词： branched-chain amino acids cardiovascular health circadian clock drosophila insulin metabolism sleep γ-aminobutyric acid

Tale of mitochondria and mitochondria-associated ER membrane in patient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry Timothy Barrett Sovan Sarkar I-STEM CECSCorbeil-EssonnesFrance UniversitéParis-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and Genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver

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Journal of Molecular Cell Biology 2016年第2期8卷 129-143页

作者： Pierre Theurey Emily Tubbs Guillaume Vial Julien Jacquemetton Nadia Bendridi Marie-Agnes Chauvin Muhammad Rizwan Alam Muriel Le Romancer Hubert Vidal Jennifer Rieusset inserm umr-1060 CarMeN LaboratoryLyon 1 UniversityINRA U1235INSA of LyonRockefeller and Charles Merieux Lyon-Sud medical UniversitiesF-69003 LyonFrance Cancer Research Center of Lyon Centre Leon BerardUMR INSERM 1052CNRS 5286F-69373 LyonFrance Hospices Civils de Lyon Lyon-Sud HospitalEndocrinologyDiabetology and Nutrition ServiceF-69310 Pierre BeniteFrance

Mitochondria-associated endoplasmic reticulum membranes(MAM)play a key role in mitochondrial dynamics and function and in hepatic insulin *** mitochondria are important regulators of energy metabolism,the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are *** this study,we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse *** of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in *** reduced organelle interactions through the pentose phosphate-protein phosphatase 2A(PP-PP2A)pathway,induced mitochondria fission,and impaired *** MAM reduction counteracted glucose-induced mitochondrial ***,disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and *** glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice,both characterized by chronic disruption of MAM integrity,mitochondrial fission,and altered mitochondrial *** data indicate that MAM contribute to the hepatic glucose-sensing system,allowing regulation of mitochondria dynamics and function during nutritional *** disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance.

关键词： MAM mitochondria dynamics hepatocytes glucose sensing pentose phosphate pathway PP2A

Click and bioorthogonal hyaluronic acid hydrogels as an ultra-tunable platform for the investigation of cell-material interactions

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Bioactive Materials 2023年第6期24卷 438-449页

作者： Nathan Lagneau Pierre Tournier Boris Halgand François Loll Yves Maugars Jérôme Guicheux Catherine Le Visage Vianney Delplace Nantes Université OnirisCHU NantesINSERMRegenerative Medicine and SkeletonRMeSUMR 1229F-44000France

The cellular microenvironment plays a major role in the biological functions of ***,biomaterials,especially hydrogels,which can be design to mimic the cellular microenvironment,are being increasingly used for cell encapsulation,delivery,and 3D culture,with the hope of controlling cell ***,much remains to be understood about the effects of cell-material interactions,and advanced synthetic strategies need to be developed to independently control the mechanical and biochemical properties of *** address this challenge,we designed a new hyaluronic acid(HA)-based hydrogel platform using a click and bioorthogonal strain-promoted azide-alkyne cycloaddition(SPAAC)*** approach facilitates the synthesis of hydrogels that are easy to synthesize and sterilize,have minimal swelling,are stable long term,and are *** provides bioorthogonal HA gels over an uncommonly large range of stiffness(0.5-45 kPa),all forming within 1-15 *** importantly,our approach offers a versatile one-pot procedure to independently tune the hydrogel composition(e.g.,polymer and adhesive peptides).Using this platform,we investigate the independent effects of polymer type,stiffness,and adhesion on the secretory properties of human adipose-derived stromal cells(hASCs)and demonstrate that HA can enhance the secretion of immunomodulatory factors by hASCs.

关键词： Hydrogels Click and bioorthogonal chemistry Hyaluronic acid Mesenchymal stromal cells Cell-material interactions Secretome

Inhibition of mitochondrial fatty acid oxidation in drug-induced hepatic steatosis

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Liver Research 2019年第3期3卷 157-169页

作者： Bernard Fromenty inserm UMR 1241Universitéde Rennes 1RennesFrance

Mitochondrial fatty acid oxidation(mtFAO)is a key metabolic pathway required for energy production in the liver,in particular during periods of *** major consequence of drug-induced impairment of mtFAO is hepatic steatosis,which is characterized by an accumulation of triglycerides and other lipid species,such as ***,the severity of this liver lesion is dependent on the residual mitochondrial b-oxidation ***,a severe inhibition of mtFAO leads to microvesicular steatosis,hypoglycemia and liver *** contrast,moderate impairment of mtFAO can cause macrovacuolar steatosis,which is a benign lesion in the short *** some drugs can induce both microvesicular and macrovacuolar steatosis,it is surmised that severe mitochondrial dysfunction could be favored in some patients by non-genetic factors(e.g.,high doses and polymedication),or genetic predispositions involving genes that encode proteins playing directly or indirectly a role in the mtFAO *** of drugs inducing steatosis include acetaminophen(APAP),amiodarone,ibuprofen,linezolid,nucleoside reverse transcriptase inhibitors,such as stavudine and didanosine,perhexiline,tamoxifen,tetracyclines,troglitazone and valproic *** several previous articles reviewed in depth the mechanism(s)whereby most of these drugs are able to inhibit mtFAO and induce steatosis,the present review is rather focused on APAP,linezolid and *** steatogenic drugs are indeed rarely discussed in the literature as regards their ability to impair mtFAO.

关键词： Drug-induced liver injury(DILI) Steatosis Mitochondria b-Oxidation Acetaminophen(APAP) Troglitazone

Autophagy in dendritic cells

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Cellular & Molecular Immunology 2018年第11期15卷 944-952页

作者： Ghita Ghislat Toby Lawrence Centre d‘Immunologie de Marseille-Luminy InsermU1104CNRS UMR7280MarseilleFrance

Autophagy and immunity share the property of being auto-protective for the *** is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to *** in autophagy are associated with inflammation and cancer *** studies have characterized the molecular details regarding how autophagy is controlled by immune *** these,dendritic cells(DCs)are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and *** undergo functional maturation that can either lead to an immunostimulatory phenotype,as in the context of infection,or to a tolerogenic phenotype associated with immunosuppression to self-antigens,as well as to *** increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological ***,we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.

关键词： autophagy dendritic cells maturation

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

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Neural Regeneration Research 2017年第9期12卷 1418-1421页

作者： Laura Foucault-Fruchard Daniel Antier umr inserm U930 Université Fran?ois Rabelais CHRU de Tours H?pital Bretonneau

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

关键词： α7 nicotinic receptors cholinergic anti-inflammatory pathway Alzheimer's disease Huntington's disease Parkinson's disease neuroinflammation neurodegeneration positive allosteric modulators