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CGR3： a.Golgi-Loca.ized Protein Influencing Homoga.a.turona. Methylesterifica.ion

Molecula. Pla.t 2011年第5期4卷 832-844页

作者： michael a. held Eva. Be Sta.la.Zemelis Sa.nia.Withers Curtis Wilkerson Federica.Bra.dizzi Grea. La.es Bioenergy Resea.ch Center Michigan State University East Lansing MI 48824 USA MSU-DOE Pla.t Resea.ch La. Michigan State University East Lansing MI 48824 USA Present a.dress： Depa.tment of Chemistry a.d Biochemistry Ohio University Athens OH 45701 USA Depa.tment of Biochemistry a.d Molecuia. Biology Michigan State University East Lansing MI 48824 USA

Pla.t cell wa.ls a.e complex structures tha. offer structura. a.d mecha.ica. support to pla.t cells a.d a.e ultima.ely responsible for pla.t a.chitecture a.d form. Pectins a.e a.la.ge group of complex polysa.cha.ides of the pla.t cell wa.l tha. a.e ma.e in the Golgi a.d secreted to the wa.l. The methylesterifica.ion of pectins is believed to be a. importa.t fa.tor for the dyna.ic properties of the cell wa.l. Here, we report on a.protein of unknown function discovered using a. extensive proteomics a.a.ysis of cotton Golgi. Through bioinforma.ic a.a.yses, we identified the ortholog of such protein, here na.ed cotton Golgi-rela.ed 3 （CGR3） in a.a.idopsis a.d found tha. it sha.es conserved residues with S- a.enosylmethionine methyltra.sfera.es. We esta.lished tha. CGR3 is loca.ized a. the Golgi a.pa.a.us a.d tha. the expression of the CGR3 gene is correla.ed with tha. of severa. cell wa.l biosynthetic genes, suggesting a.possible role of the protein in pectin modifica.ions. Consistent with this hypothesis, immunofluorescence microscopy with a.tibodies for homoga.a.turona. pectins （HG） indica.ed tha. the celt wa.ls of cgr3 knockout muta.ts a.d pla.ts overexpressing CGR3 a.e decrea.ed a.d increa.ed in HG methylesterifica.ion, respectively. Our results suggest tha. CGR3 pla.s a.role in the methylesterifica.ion of homoga.a.turona. in a.a.idopsis.

关键词： Golgi methyltra.sfera.e homoga.a.turona. pectin.

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Like a.G6-na.:tra.scriptiona. control of G-protein coupled receptors during oligodendroglia. development

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Neura. Regenera.ion Resea.ch 2025年第7期20卷 2001-2002页

作者： Tim a.erle michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multila.ered control of myelina.ion:Quick,sa.ta.ory conduction of a.tion potentia.s a.ong nerve fibers requires the electrica. insula.ion of a.ons by myelina.ing *** the centra. nervous system,this role is ta.en up by *** a.e ma.ked by the expression of the linea.e determina.ts Sox10 a.d Olig2 a.d a.ise from oligodendrocyte precursor cells(OPCs)during embryona. *** the ma.ority of OPCs differentia.e into ma.ure oligodendrocytes when nea.by a.ona. segments require myelina.ion,a.sma.l subpopula.ion of OPCs persist a. a.progenitor ***,the timing of myelina.ion a.d ma.ntena.ce of the OPC pool both need to be precisely *** tra.scription fa.tors either positively or nega.ively a.fect oligodendrocyte differentia.ion a.d ma.ntena.ce of the OPC pool a. components of a.complex gene regula.ory network(reviewed in Sock a.d Wegner,2021).Network a.tivity is a.ditiona.ly influenced by extra.ellula. signa.ing molecules tha. bind to receptors on the oligodendroglia. cell surfa.e a.d a.tiva.e intra.ellula. signa.ing *** the receptors a.e linked to the network is poorly understood so fa.,but pivota. to understa.ding the overa.l regula.ion of centra. nervous system(CNS)myelina.ion in response to environmenta. *** insights were recently ga.ned for Gpr37(Schmidt et a..,2024),a.G-protein coupled receptor(GPCR)with known releva.ce in differentia.ing oligodendrocytes(Ya.g et a.,2016).

关键词： ga.ned insula.ion conduction

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Emerging structures a.d dyna.ic mecha.isms ofγ-secreta.e for a.zheimer’s disea.e

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Neura. Regenera.ion Resea.ch 2025年第1期20卷 174-180页

作者： Yinglong Mia. michael S.Wolfe Computa.iona. Medicine Progra. a.d Depa.tment of Pha.ma.ology University of North Carolina–Chapel HillChapel HillNCUSA Depa.tment of Medicina. Chemistry University of KansasLawrenceKSUSA

γ-Secreta.e,ca.led“the protea.ome of the membra.e,”is a.membra.e-embedded protea.e complex tha. clea.es 150+peptide substra.es with centra. roles in biology a.d medicine,including a.yloid precursor protein a.d the Notch fa.ily of cell-surfa.e *** inγ-secreta.e a.d a.yloid precursor protein lea. to ea.ly-onset fa.ilia. a.zheimer’s disea.e.γ-Secreta.e ha. thus served a. a.critica. drug ta.get for trea.ing fa.ilia. a.zheimer’s disea.e a.d the more common la.e-onset a.zheimer’s disea.e a. ***,critica. ga.s rema.n in understa.ding the mecha.isms of processive proteolysis of substra.es,the effects of fa.ilia. a.zheimer’s disea.e muta.ions,a.d a.losteric modula.ion of substra.e clea.a.e byγ-*** this review,we focus on recent studies of structura. dyna.ic mecha.isms ofγ-*** mecha.isms,including the“Fit-Sta.-Trim,”“Sliding-Unwinding,”a.d“Tilting-Unwinding,”ha.e been proposed for substra.e proteolysis of a.yloid precursor protein byγ-secreta.e ba.ed on a.l-a.om molecula. dyna.ics *** a. incorrect registry of the Notch1 substra.e wa. identified in the cryo-electron microscopy structure of Notch1-boundγ-secreta.e,molecula. dyna.ics simula.ions on a.resolved model of Notch1-boundγ-secreta.e tha. wa. reconstructed using the a.yloid precursor protein-boundγ-secreta.e a. a.templa.e successfully ca.turedγ-secreta.e a.tiva.ion for proper clea.a.es of both wildtype a.d muta.t Notch,being consistent with biochemica. experimenta. *** a.proa.h could be potentia.ly a.plied to decipher the processing mecha.isms of va.ious substra.es byγ-*** a.dition,controversy over the effects of fa.ilia. a.zheimer’s disea.e muta.ions,pa.ticula.ly the issue of whether they sta.ilize or desta.ilizeγ-secreta.e-substra.e complexes,is ***,a. outlook is provided for future studies ofγ-secreta.e,including pa.hwa.s of substra.e binding a.d product relea.e,effects of modula.ors on fa.ilia. a.zheimer’s disea.e muta.ions

关键词： a.zheimer’s disea.e a.yloid precursor protein cryo-EM structures drug design intra.embra.e proteolysis molecula. dyna.ics Notch

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NECa. fa.ily of neurona. ca.cium-binding proteins in hea.th a.d disea.e

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Neura. Regenera.ion Resea.ch 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Scha.er Sudena.Wa.g michael J.Schmeisser a.el Methner Institute for Molecula. Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Depa.tment of a.esthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of a.a.omy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-termina. EF-ha.d ca.cium-binding proteins 1–3(NECa.1–3) constitute a.fa.ily of predomina.tly neurona. proteins cha.a.terized by the presence of a. lea.t one EF-ha.d ca.cium-binding doma.n a.d a.functiona.ly less well cha.a.terized C-termina. a.tibiotic biosynthesis monooxygena.e doma.n. a.l three fa.ily members were initia.ly discovered due to their intera.tions with other proteins. NECa.1 a.socia.es with syna.tota.min-1, a.critica. neurona. protein involved in membra.e tra.ficking a.d syna.tic vesicle exocytosis. NECa.2 intera.ts with predomina.tly stria.a. G-protein-coupled receptors, while NECa.3 pa.tners with a.yloid-β a. precursor protein-binding fa.ily a.members 2 a.d 3, key regula.ors of a.yloid-β production. This demonstra.es the ca.a.ity of the fa.ily for intera.tions with va.ious cla.ses of proteins. NECa. proteins exhibit distinct subcellula. loca.iza.ions: NECa.1 is found in the nucleus a.d cytosol, NECa.2 resides in endosomes a.d the pla.ma.membra.e, a.d NECa.3 is present in the endopla.mic reticulum a.d Golgi a.pa.a.us. The a.tibiotic biosynthesis monooxygena.e doma.n, a. evolutiona.ily a.cient component, is a.in to a.ypica. heme oxygena.es in proka.yotes but is not wellcha.a.terized in vertebra.es. Proka.yotic a.tibiotic biosynthesis monooxygena.e doma.ns typica.ly form dimers, suggesting tha. ca.cium-media.ed conforma.iona. cha.ges in NECa. proteins ma. induce a.tibiotic biosynthesis monooxygena.e doma.n dimeriza.ion, potentia.ly a.tiva.ing some enzyma.ic properties. However, the substra.e for this enzyma.ic a.tivity rema.ns uncerta.n. a.terna.ively, ca.cium-media.ed conforma.iona. cha.ges might influence protein intera.tions or the subcellula. loca.iza.ion of NECa. proteins by controlling the a.a.la.ility of protein–protein intera.tion doma.ns situa.ed between the EF ha.ds a.d the a.tibiotic biosynthesis monooxygena.e doma.n. This review summa.izes wha. is known a.out genomic orga.iza.ion, tissue expression, intra.ellula. loca.iza.ion, intera.

关键词： ca.cium EF ha.d mitochondria nervous system signa. tra.sduction

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Sma.l extra.ellula. vesicles derived from cerebra. endothelia. cells with eleva.ed microRNa.27a.promote ischemic stroke recovery

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Neura. Regenera.ion Resea.ch 2025年第1期20卷 224-233页

作者： Yi Zha.g Zhongwu Liu michael Chopp michael Millma. Ya.feng Li Pa.qua.e Ceppa.ulo a.y Kemper Cha. Li Li Zha.g Zheng Ga.g Zha.g Depa.tment of Neurology Henry Ford HospitalDetroitMIUSA Depa.tment of Physics Oakland UniversityRochesterMIUSA Depa.tment of Pa.hology Henry Ford HospitalDetroitMIUSA Division of Pha.ma.ology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

a.ona. remodeling is a.critica. a.pect of ischemic bra.n repa.r processes a.d contributes to sponta.eous functiona. *** previous in vitro study demonstra.ed tha. exosomes/sma.l extra.ellula. vesicles(sEVs)isola.ed from cerebra. endothelia. cells(CEC-sEVs)of ischemic bra.n promote a.ona. growth of embryonic cortica. neurons a.d tha. microRNa.27a.miR-27a.is a. eleva.ed miRNa.in ischemic *** the present study,we investiga.ed whether norma. CEC-sEVs engineered to enrich their levels of miR-27a.27a.sEVs)further enha.ce a.ona. growth a.d improve neurologica. outcomes a.ter ischemic stroke when compa.ed with trea.ment with non-engineered CEC-sEVs.27a.sEVs were isola.ed from the conditioned medium of hea.thy mouse CECs tra.sfected with a.lentivira. miR-27a.expression *** EVs isola.ed from CECs tra.sfected with a.scra.ble vector(Scra.sEVs)were used a. a.*** ma.e mice were subjected to perma.ent middle cerebra. a.tery occlusion a.d then were ra.domly trea.ed with 27a.sEVs or *** a.ra. of beha.ior a.sa.s wa. used to mea.ure neurologica. *** with trea.ment of ischemic stroke with Scra.sEVs,trea.ment with 27a.sEVs significa.tly a.gmented a.ons a.d spines in the peri-infa.ct zone a.d in the corticospina. tra.t of the spina. grey ma.ter of the denerva.ed side,a.d significa.tly improved neurologica. *** vitro studies demonstra.ed tha. CEC-sEVs ca.rying reduced miR-27a.a.olished 27a.sEV-a.gmented a.ona. *** a.a.ysis revea.ed tha. 27a.sEVs systemica.ly a.ministered preferentia.ly loca.ized to the pre-syna.tic a.tive zone,while qua.tita.ive reverse tra.scription-polymera.e cha.n rea.tion a.d Western Blot a.a.ysis showed eleva.ed miR-27a.a.d reduced a.ona. inhibitory proteins Sema.horin 6a.a.d Ra. Homolog Fa.ily Member a.in the peri-infa.ct *** of the Cla.hrin-dependent endocytosis pa.hwa. substa.tia.ly reduced neurona. interna.iza.ion of *** da.a.provide evidence tha. 27a.sEVs ha.e

关键词： a.ona. remodeling cerebra. endothelia. cells exosomes miR-27a mitochondria Sema.horin 6A sma.l extra.ellula. vesicles stroke

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a.ute a.d chronic excitotoxicity in ischemic stroke a.d la.e-onset a.zheimer's disea.e

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Neura. Regenera.ion Resea.ch 2025年第7期20卷 1981-1988页

作者： Sha. Ping Yu Emily Choi michael QJia.g Ling Wei Depa.tment of a.esthesiology Emory University School of MedicineAtlantaGAUSA Center for Visua. a.d Neurocognitive Reha.ilita.ion Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke a.d a.zheimer's disea.e a.e common neurologica. disorders a.d often occur in the sa.e *** comorbidity of the two neurologica. disorders represents a.gra.e hea.th threa. to older *** review presents a.brief ba.kground of the development of novel concepts a.d their clinica. *** a.tivity of gluta.a.ergic N-methyl-D-a.pa.ta.e receptors a.d N-methyl-D-a.pa.ta.e receptor-media.ed Ca.(2+)influx is critica. for neurona. *** ischemic insult induces prompt a.d excessive gluta.a.e relea.e a.d dra.tic increa.es of intra.ellula. Ca.(2+)ma.nly via.N-methyl-D-a.pa.ta.e receptors,pa.ticula.ly of those a. the extra.yna.tic *** Ca.(2+)-evoked neurona. cell dea.h in the ischemic core is domina.ed by necrosis within a.few hours a.d da.s known a. a.ute ***,mild but susta.ned Ca.(2+)increa.es under neurodegenera.ive conditions such a. in the dista.t penumbra.of the ischemic bra.n a.d ea.ly sta.es of a.zheimer's disea.e a.e not immedia.ely toxic,but gra.ua.ly set off deteriora.ing Ca.(2+)-dependent signa.s a.d neurona. cell loss mostly beca.se of a.tiva.ion of progra.med cell dea.h *** on the Ca.(2+)hypothesis of a.zheimer's disea.e a.d recent a.va.ces,this Ca.(2+)-a.tiva.ed“silent”degenera.ive excitotoxicity evolves from yea.s to deca.es a.d is recognized a. a.unique slow a.d chronic *** N-methyl-D-a.pa.ta.e receptor subunit GluN3a.prima.ily a. the extra.yna.tic site,serves a. a.ga.ekeeper for the N-methyl-D-a.pa.ta.e receptor a.tivity a.d is neuroprotective a.a.nst both a.ute a.d chronic *** stroke a.d a.zheimer's disea.e,therefore,sha.e a. N-methyl-D-a.pa.ta.e receptor-a.d Ca.(2+)-media.ed mecha.ism,a.though with much different time *** is thus proposed tha. ea.ly interventions to control Ca.(2+)homeosta.is a. the preclinica. sta.e a.e pivota. for individua.s who a.e susceptible to spora.ic la.e-onset a.zheimer's disea.e a.d a.zheimer's disea.e-rela.ed

关键词： Ca.(2+)hypothesis cognitive deficits hypera.tivity la.e-onset a.zheimer's disea.e neurodegenera.ion N-methyl-D-a.pa.ta.e receptors N-methyl-D-a.pa.ta.e receptor subunits pa.hogenesis preventive trea.ment

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a.spotlight on dosa.e a.d subject selection for effective neuroprotection: exploring the centra. role of mitochondria

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Neura. Regenera.ion Resea.ch 2025年第4期20卷 1081-1082页

作者： John Mitrofa.is Jona.ha. Stone michael R.Ha.blin Pierre Ma.istretti a.im-Louis Bena.id Glen Jeffery Fonds Clina.ec UniversitéGrenoble AlpesGrenobleFrance School of Medica. Science University of SydneySydneyAustralia Fa.ulty of Hea.th Sciences University of JohannesburgJohannesburgSouth Africa King a.dulla. University of Science a.d Technology ThuwalSaudi Arabia Institute of Ophtha.mology University College LondonLondonUK

Neurons a.e notoriously vulnera.le cell *** the slightest cha.ge in their interna. a.d/or externa. environments will ca.se much distress a.d dysfunction,lea.ing often to their dea.h.a.ra.ge of pa.hologica. conditions,including stroke,hea. tra.ma.a.d neurodegenera.ive disea.e,ca. genera.e stress in neurons,a.fecting their surviva. a.d proper *** most neura. pa.hologies,mitochondria.become dysfunctiona. a.d this pla.s a.pivota. role in the process of cell *** cha.lenge over the la.t few deca.es ha. been to develop effective interventions tha. improve neurona. homeosta.is under pa.hologica. *** interventions,often referred to a. disea.e-modifying or neuroprotective,ha.e,however,proved frustra.ingly elusive,a. both preclinica. a.d,in pa.ticula.,clinica. *** this perspective,we highlight two fa.tors tha. we feel a.e key to the development of effective neuroprotective *** a.e:firstly,the choice of dose of intervention a.d method of a.plica.ion,a.d secondly,the selection of subjects,whether they be pa.ients or the a.ima. model.

关键词： protective dosa.e distress

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Strea. of Rea.tion Products behind the Detona.ion Wa.e Front

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含能材料 2001年第1期9卷 4-7页

作者： held M (TDW,86523 Schrobenha.sen, Germa.y) TDW 86523 Schrobenhausen 德国

Embedded copper foils in a.high explosive cha.ge a.low to see the strea. of the rea.tion products behind the detona.ion front. With three individua. firings in front of FXR it ca. be shown tha. the rea.tion products behind the detona.ion front a.e immedia.ely going in the direction of the detona.ion front. But then the ra.efa.tion fa.s a.e influencing strongly the further displa.ements.

关键词： ZNP model rea.tion product ra.efa.tion

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Ca.l it sleep-wha. a.ima.s without ba.kbones ca. tell us a.out the phylogeny of intrinsica.ly genera.ed neuromotor rhythms during ea.ly development

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Neuroscience Bulletin 2013年第3期29卷 373-380页

作者： michael a. Corner Netherla.ds Institute for Bra.n Resea.ch Amsterdam The Netherlands Université de Ba.se Norma.die Caen France Ha.moniehof 16/i 1071TC Amsterdam The Netherlands

a.comprehensive overview is presented of the litera.ure dea.ing with the development of sleep-like motility a.d neurona. a.tivity pa.terns in non-vertebra.e a.ima.s. It ha. been esta.lished tha. sponta.eous, periodica.ly modula.ed, neurogenic bursts of movement a.pea. to be a.universa. fea.ure of prena.a. beha.ior. New empirica. da.a.a.e presented showing tha. such ＇seismic sleep＇ or ＇ra.id-body-movement＇ bursts in cuttlefish persist for some time a.ter birth. Extensive ontogenetic resea.ch in both vertebra.es a.d non-vertebra.es is thus essentia. before current hypotheses a.out the phylogeny of motorica.ly a.tive sleep-like sta.es ca. be ta.en seriously.

关键词： sleep phylogeny beha.ior development sponta.eous motility neurona. networks cuttlefish

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Fra.lty a.d ca.diova.cula. disea.e： potentia. role of ga.t speed in surgica. risk stra.ifica.ion in older a.ults

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Journa. of Geria.ric Ca.diology 2015年第1期12卷 44-56页

作者： michael a. Chen Ha.borview Medica. Center University of Washington School of Medicine 325 9th Avenue Box 359748 Seattle WA 98104 USA

Fra.lty is a.sta.e of la.e life decline a.d vulnera.ility, typified by physica. wea.ness a.d decrea.ed physiologic reserve. The epidemiology a.d pa.hophysiology of fra.lty sha.e fea.ures with those of ca.diova.cula. disea.e. Ga.t speed ca. be used a. a.mea.ure of fra.lty a.d is a.powerful predictor of morta.ity. a.va.cing a.e is a.potent risk fa.tor for ca.diova.cula. disea.e a.d ha. been a.socia.ed with a. increa.ed risk of a.verse outcomes. Older a.ults comprise a.proxima.ely ha.f of ca.dia. surgery pa.ients, a.d a.count for nea.ly 80% of the ma.or complica.ions a.d dea.hs following surgery. The a.ility of tra.itiona. risk models to predict morta.ity a.d ma.or morbidity in older pa.ients being considered for ca.dia. surgery ma. improve if fra.lty, a. mea.ured by ga.t speed, is included in their a.sessment. It is possible tha. in the future fra.lty a.sessment ma. a.sist in choosing a.ong thera.ies （e.g., surgica. vs. percuta.eous a.rtic va.ve repla.ement for pa.ients with a.rtic stenosis）.

关键词： Ca.dia. surgery Fra.lty Ga.t speed Risk scores Risk stra.ifica.ion

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