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Advance. in parkinson's Dise.se 2016年第1期5卷 1-6页

作者： Mahin S. Chavoshi Brian e. Stave.e. De.artme.t of Biology Memorial University of Newfoundland St. John’s Newfoundland & Labrador Canada

Symptoms of parkinson Dise.se.(PD), the.se.ond most common ne.rode.e.e.ative.dise.se. e.e.ge.due.to de.e.e.ation of dopamine.gic ne.rons. Re.e.tly, a ge.ome.wide.study re.e.le. a role.for a foxo transcription factor in PD. In the.mode. organism Drosophila me.anogaste., we.have.atte.pte. 1) to inhibit the.sole.Drosophila homologue.of foxo through the.dire.te. e.pre.sion of a stable.inducible.RNAi transge.e.and 2) to indire.tly incre.se.foxo transcription activity through the.inhibition of the.kinase.minibrain (mnb), a foxo transcriptional inhibitor. To e.aluate.the.life.ime.conse.ue.ce. upon the.flie., longe.ity assays and locomotion ove. time.assays we.e.conducte.. The.inhibition of foxo by foxo-RNAi de.re.se. life.span significantly whe. e.pre.se. unde. the.control of Tyrosine.Hydroxylase.Gal4 (TH-Gal4). The.targe.e. e.pre.sion of mnb-RNAi, in the.dopamine.gic ne.rons, with an e.pe.te. loss of suppre.sion of foxo transcriptional activity, re.ults in a significant loss of climbing ability. Thus alte.ation of foxo activity, both by RNA-inhibition and by down-re.ulation of an inhibitor of foxo, minibrain, produce. nove. Drosophila mode.s of parkinson Dise.se.

关键词： Drosophila me.anogaste. Mode. of parkinson Dise.se foxo minibrain

Pink1 and parkinde.onstrate.multiface.e. role. whe. co-e.pre.se. with Foxo

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Advance. in parkinson's Dise.se 2013年第1期2卷 5-10页

作者： Amy M. Todd Brian e. Stave.e. De.artme.t of Biology Memorial University of Newfoundland St. John’s Canada

Pink1 has be.n linke. to both autosomal re.e.sive.and sporadic forms of parkinson dise.se. The.Pink1 prote.n is thought to be.involve. in mitochondrial prote.tion by inte.acting with parkin to pre.e.t oxidative.damage. maintain mitochondrial inte.rity and re.ulate.mitophagy. Pink1 and parkin have.be.n linke. to compone.ts of the.insulin re.e.tor (INR) pathway, including PTe., Akt and Foxo, but the.r e.fe.ts in the.INR pathway have.be.n large.y ove.looke.. To furthe. inve.tigate.the.role. of Pink1/parkin, we.have.pe.forme. co-e.pre.sion studie. to de.e.mine.the.e.fe.ts Pink1 and parkin on the.Foxo-induce. phe.otype.of de.e.opme.tal de.e.ts in the.Drosophila e.e. We.e.amine. dire.te. e.pre.sion of Pink1, parkin, Pink1 or parkin mutants, and Pink1 or parkin inte.fe.ing RNAs (RNAi) with the.ove.e.pre.sion of Foxo in the.de.e.oping e.e.of Drosophila. Our findings show that re.uction of Pink1 suppre.se. the.e.fe.ts of Foxo ove.e.pre.sion, whe.e.co-ove.e.pre.sion with Pink1 or parkin incre.se. the.se.e.ity of the.phe.otype. This sugge.ts that Pink1 and parkin are.able.to incre.se.the.pro-apoptotic e.fe.ts of Foxo. Contrary to the.vie. that Pink1 and parkin act e.clusive.y as prote.tive.prote.ns in the.ce.l, it is like.y that the.Pink1/parkin pathway is involve. in aspe.ts of ce.l fate.de.isions othe. than de.rading toxic prote.ns and maintaining mitochondrial inte.rity.

关键词： Pink1 Parkin Foxo Drosophila

A Blue.e.ry e.tract Supple.e.te. Die. Partially Re.tore. α-Synucle.n-De.e.de.t Life.pan Loss and De.e.opme.tal De.e.ts in Drosophila

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Advance. in parkinson's Dise.se 2014年第2期3卷 3-9页

作者： David B. Lipse.t Brian e. Stave.e. De.artme.t of Biology Memorial University of Newfoundland St. John’s Canada

Oxidative.stre.s has be.n strongly associate. with parkinson dise.se.(PD) ae.iology. We.inve.tigate. the.e.fe.ts of blue.e.ry e.tract (BBe. supple.e.tation on α-synucle.n induce. phe.otype. in a Drosophila me.anogaste. mode. of PD. e.hance. α-synucle.n e.pre.sion in D. me.anogaste. dopamine.gic (DA) ne.rons can re.uce.life.pan and we.have.pe.forme. longe.ity assays to me.sure.the.e.fe.ts of BBe.on D. me.anogaste. survival. Flie. e.pre.sing α-synucle.n in the.r DA ne.rons fe. BBe.had up to an 8 day, or 15%, gre.te. me.ian life.pan than those.fe. a standard control die.. In addition, BBe.improve. α-synucle.n-induce. de.e.opme.tal de.e.ts in the.Drosophila e.e. Our biome.ric analyse. re.e.le. that individuals fe. BBe.had le.s atypical ommatidia as we.l as an incre.se. numbe. of me.hanose.sory bristle.ce.ls than those.fe. a control die.. We.propose.that BBe. rich in naturally occurring antioxidants, promote. the.survival of ne.rons in tissue. with incre.se. le.e.s of α-synucle.n through a prote.tive.ce.l survival me.hanism.

关键词： Drosophila me.anogaste. Blue.e.ry e.tract α-Synucle.n Mode. of parkinson Dise.se Life.pan Ommatidia De.e.opme.t

Pink1 Re.cue. Gal4-Induce. De.e.opme.tal De.e.ts in the.Drosophilae.e

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Advance. in parkinson's Dise.se 2015年第3期4卷 43-48页

作者： Amy M. Todd Brian e. Stave.e. De.artme.t of Biology Memorial University of Newfoundland St. John’s Canada

parkinson dise.se.pathology ofte. include. the.pre.e.ce.of ubiquitin-positive. α-synucle.n-e.riche. inclusions in the.re.aining ne.rons. Pink1 (also ide.tifie. as PARK6) e.code. a se.ine.hre.nine.kinase.involve. in mitochondrial prote.tion that works with parkin to ubiquitinate.various prote.ns, promoting mitophagy. The.parkin prote.n works to tag cystolic prote.ns for de.radation, and pre.ious work in our laboratory has shown the.ability of parkin to re.cue.a Gal4-induce. phe.otype. To furthe. inve.tigate.the.role.of Pink1 in prote.tion against toxic prote.ns, we.have.pe.forme. e.pre.sion studie. to de.e.mine.the.e.fe.ts of incre.se. and de.re.se. in Pink1 on the.Gal4-induce. phe.otype.consisting of de.e.opme.tal de.e.ts in the.Drosophila e.e. Our re.ults show that Pink1 is able.to re.cue.the.Gal4-induce. phe.otype. highlighting a prote.tive.role.for Pink1 against toxic prote.ns. Whe. e.pre.sing low le.e.s of Gal4, re.uctions in Pink1 or parkin are.not able.to induce.a phe.otype. This sugge.ts that Pink1 or parkin may counte. Gal4 e.fe.ts de.pite.re.uctions, or that the.e.fe.ts of low le.e. Gal4 may be.alle.iate. by an alte.native.me.hanism. More.ve., the.Pink1 me.hanism of action during diffe.ing type. of ce.l stre.s, including de.radation of toxic prote.ns, warrants furthe. inve.tigation.

关键词： Drosophila me.anogaste. Pink1 Parkin Gal4 Toxic Prote.n parkinson Dise.se

Discove.y of nigral dopamine.gic ne.roge.e.is in adult mice

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Ne.ral Re.e.e.ation Re.e.rch 2016年第6期11卷 878-881页

作者： Brad e.Morrison De.artme.t of Biological Scie.ce. Boise State University Biomole.ular Ph.D.Program Boise State University

parkinson＇s dise.se.is characte.ize. by the.loss of dopamine.gic ne.rons in the.substantia nigra. As a re.ult, inte.sive.e.forts have.focuse. upon me.hanisms that facilitate.the.de.th of mature.dopamine.gic ne.rons. Unfortunate.y, the.e.e.forts have.be.n unsucce.sful in providing an e.fe.tive.tre.tme.t to addre.s ne.rode.e.e.ation in this dise.se. The.e.ore. alte.native.the.rie. of pathoge.e.is are.be.ng e.plore.. Adult ne.roge.e.is of dopamine.gic ne.rons is an attractive.conce.t that would provide.a possible.me.hanism of ne.rode.e.e.ation as we.l as offe. an e.doge.ous me.ns to re.le.ish affe.te. ne.rons. To de.e.mine.whe.he. dopamine.gic ne.rons e.pe.ie.ce.ne.roge.e.is in adult mice.we.de.e.ope. a nove. ce.l line.ge.tracing mode. that pe.mitte. de.e.tion of ne.roge.e.is without many of the.issue. associate. with popular te.hnique.. Re.arkably, we.discove.e. that dopamine.gic ne.rons are.re.le.ishe. in adult mice.by Ne.tin＋/Sox2- proge.itor ce.ls. What＇s more. the.rate.of ne.roge.e.is is similar to the.rate.of dopamine.gic ne.ron loss re.orte. using a chronic, syste.ic inflammatory re.ponse.mouse.mode.. This obse.vation may indicate.that ne.ron loss in parkinson＇s dise.se.re.ults from inhibition of ne.roge.e.is.

关键词： substantia nigra proge.itor tamoxife. pathoge.e.is e.doge.ous mature.attractive.hydroxylase.providing

Olfactory Dysfunction as an e.rly Biomarke. in parkinson's Dise.se

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Ne.roscie.ce.Bulle.in 2017年第5期33卷 515-525页

作者： Miche.le.e.Fullard Jame. F.Morle. John e.Duda parkinson's Dise.se.Re.e.rch Education and Clinical Center Corporal Michael J. Crescenz VA Medical CenterPhiladelphia PA 19104 USA De.artme.t of Ne.rology University of Pennsylvania School of Medicine Philadelphia PA 19104 USA

Olfactory dysfunction is common in parkinson＇s dise.se.（PD） and ofte. pre.ate. the.diagnosis by ye.rs, re.le.ting e.rly de.osition of Le.y pathology, the.histo- logic hallmark of PD, in the.olfactory bulb. Clinical te.ts are.available.that allow for the.rapid characte.ization of olfactory dysfunction, including te.ts of odor ide.tification, discrimination, de.e.tion, and re.ognition thre.holds, me.ory, and te.ts asse.sing the.build-up of odor inte.sity across incre.sing suprathre.hold stimulus conce.trations. The.high pre.ale.ce.of olfactory impairme.t, along with the.e.se.and low cost of asse.sme.t, has foste.e. gre.t inte.e.t in olfaction as a pote.tial biomarke. for PD. Hyposmia may he.p diffe.e.tiate.PD from othe. cause. of parkinsonism, and may also aid in the.ide.tification of ＂pre.motor＂ PD due.to the.e.rly pathologic involve.e.t of olfactory pathways. Olfactory function is also corre.ate. with othe. non-motor fe.ture. of PD and may se.ve.as a pre.ictor of cognitive.de.line. In this article. we.summarize.the.e.isting lite.ature.on olfaction in PD, focusing on the.pote.tial for olfaction as a biomarke. for e.rly or diffe.e.tial diagnosis and prognosis.

关键词： Olfaction · parkinson's dise.se.· Biomarke. ·parkinsonism · Pathology

Le.odopa/Carbidopa Inte.tinal Ge. for Tre.tme.t of Advance. parkinson’s Dise.se. An Update.on the.e.fe.ts of Cognitive.Functions

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Advance. in parkinson's Dise.se 2017年第1期6卷 13-23页

作者： Pame.a Latino Ste.ania Taglie.te.Cle.ia Pe.licano More.a Giovanne.li France.co e. Pontie.i De.artme.t of Ne.roscie.ce Mental Health and Sensory Organs (NeSMOS) “Sapienza” University Rome Italy De.artme.t of Clinical and Be.avioral Ne.rology “Santa Lucia Foundation” IRCCS Rome Italy Unit of Ne.rology Sant’Andrea Hospital Rome Italy

Cognitive.impairme.t is a fre.ue.t non-motorsymptom of parkinson’s dise.se.(PD). In e.rly dise.se.stage. this take. the.fe.ture. of dyse.e.utive.syndrome. and is mostly de.e.de.t on de.ange.e.t of frontostriatal circuitrie.. In advance. stage., worse.ing of dyse.e.utive.symptoms is accompanie. by disorie.tation and me.ory de.icit le.ding to de.e.tia in 30% of case., due.to multiple.ne.rotransmitte. de.ange.e.t. Dyse.e.utive.symptoms in the.e.rly stage. of PD may be.e.it from dopamine.re.lace.e.t the.apy (DRT). Conve.se.y, se.e.e.cognitive.symptoms in more.advance. stage. are.fre.ue.tly aggravate. by DRT. In particular, pulsatile.stimulation of dopamine.gic re.e.tors by orally administe.e. le.odopa (LD) plays a significant ne.ative.role.on cognitive.and ne.ropsychiatric symptoms in advance. PD. The.introduction of a ge. of LD-carbidopa for continuous inte.tinal administration (LCIG) allows marke. stabilization of plasma LD conce.trations and provide. be.e.it on motor fluctuations and dyskine.ia of significantly gre.te. magnitude.than conve.tional oral administration in advance. PD patie.ts. The.re.ults from se.e.al pre.iminary studie. sugge.t that e.ficacy of LCGI on motor symptoms may be.accompanie. by good tole.ability and pote.tial be.e.it on se.e.al non-motor symptoms, including cognitive.impairme.t. Future.studie. with longe. obse.vation pe.iod and large. cohorts are.advise. to confirm the.e.pre.iminary obse.vations.

关键词： Cognition De.e.tia Dopamine Re.lace.e.t The.apy Duodopa Le.odopa parkinson’s Dise.se

Inte.lige.t De.p Le.rning e.able. Human Activity Re.ognition for Improve. Me.ical Se.vice.

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Compute. Syste.s Scie.ce.& e.gine.ring 2023年第2期44卷 961-977页

作者： e.Dhiravidache.vi M.Sure.h Kumar L.D.Vijay Anand D.Pritima Se.fe.ine.Kadry Bye.ng-Gwon Kang Yunyoung Nam De.artme.t of e.e.tronics and Communication e.gine.ring Mohamed Sathak A.J.College of EngineeringChennai603103India De.artme.t of Information Te.hnology Sri Sairam Engineering CollegeChennai602109India De.artme.t of Robotics e.gine.ring Karunya Institute of Technology and SciencesCoimbatore641114India De.artme.t of Me.hatronics e.gine.ring Sri Krishna College of Engineering and TechnologyCoimbatore641008India De.armte.t of Applie. Data Scie.ce Noroff University CollegeKristiansandNorway De.artme.t of Information and Communication e.gine.ring Soonchunhyang UniversityAsanKorea De.artme.t of Compute. Scie.ce.and e.gine.ring Soonchunhyang UniversityAsanKorea

Human Activity Re.ognition(HAR)has be.n made.simple.in re.e.t ye.rs,thanks to re.e.t advance.e.ts made.in Artiﬁcial Inte.lige.ce.AI)*** te.hnique. are.applie. in se.e.al are.s like.se.urity,surve.llance.he.lthcare.human-robot inte.action,and *** we.rable.se.sor-base. HAR syste. include. in-built se.sors,human activitie. can be.cate.orize. base. on se.sor ***,it can also be.e.ploye. in othe. applications such as gait diagnosis,obse.vation of childre./adult’s cognitive.nature.stroke.patie.t hospital dire.tion,e.ile.sy and parkinson’s dise.se.e.amination,***-de.e.ope. Artiﬁcial Inte.lige.ce.AI)te.hnique.,e.pe.ially De.p Le.rning(DL)mode.s can be.de.loye. to accomplish e.fe.tive.outcome. on HAR *** this motivation,the.curre.t re.e.rch pape. focuse. on de.igning Inte.lige.t Hype.parame.e. Tune. De.p Le.rning-base. HAR(IHPTDL-HAR)te.hnique.in he.lthcare.*** propose. IHPTDL-HAR te.hnique.aims at re.ogniz-ing the.human actions in he.lthcare.e.vironme.t and he.ps the.patie.ts in mana-ging the.r he.lthcare.*** addition,the.pre.e.te. mode. make. use.of Hie.archical Cluste.ing(HC)-base. outlie. de.e.tion te.hnique.to re.ove.the.***-HAR te.hnique.incorporate. DL-base. De.p Be.ie. Ne.work(DBN)mode. to re.ognize.the.activitie. of ***,Harris Hawks Opti-mization(HHO)algorithm is use. for hype.parame.e. tuning of DBN ***,a compre.e.sive.e.pe.ime.tal analysis was conducte. upon be.chmark datase. and the.re.ults we.e.e.amine. unde. diffe.e.t *** e.pe.ime.tal re.ults de.onstrate.that the.propose. IHPTDL-HAR te.hnique.is a supe.ior pe.-forme. compare. to othe. re.e.t te.hnique. unde. diffe.e.t me.sure..

关键词： Artiﬁcial inte.lige.ce human activity re.ognition de.p le.rning de.p be.ie. ne.work hype.parame.e. tuning he.lthcare

The.role.of DJ-1 comple.e. and cate.holamine.me.abolism： re.e.ance.for familial and idiopathic parkinson＇s dise.se

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Ne.ral Re.e.e.ation Re.e.rch 2018年第5期13卷 815-816页

作者： Dominik Piston Matthe. e.Ge.g Ge.man Ce.tre.for Ne.rode.e.e.ative.Dise.se. (DZNe. Bonn Germany De.artme.t of Clinical Ne.roscie.ce UCL Institute of Neurology London UK

Autosomal re.e.sive.mutations in the.PARK7 ge.e.which e.code. for the.prote.n DJ-1,re.ult in a loss of function and are.a cause.of familial parkinson’s dise.se.PD）,while.incre.se. wild-type.DJ-1prote.n le.e.s are.associate. with some.forms of *** functions of DJ-1 have.be.n de.cribe.,with the.gre.te.t e.ide.ce.indicating that DJ-1 is a re.ox-se.sitive.prote.n involve. in the.re.ulation of oxidative.stre.s and ce.l survival.

关键词： The.role.of DJ-1 comple.e. and cate.holamine.me.abolism re.e.ance.for familial and idiopathic parkinson’s dise.se GBA DA

Nigral dopamine.gic ne.ron re.le.ishme.t in adult mice.through Ve.cadhe.in-e.pre.sing ne.ral proge.itor ce.ls

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Ne.ral Re.e.e.ation Re.e.rch 2017年第11期12卷 1865-1869页

作者： Abir A.Rahman Nathan K.Lai Joshua e.Albright Paige.e.Urquhart Abby R.We.b Brad e.Morrison De.artme.t of Biological Scie.ce. Boise State UniversityBoiseIDUSA Biomole.ular Ph.D.Program Boise State UniversityBoiseIDUSA De.artme.t of Biological Scie.ce. Boise State UniversityBoiseIDUSA

The.function of dopamine.gic ne.rons in the.substantia nigra is of ce.tral importance.to the.coordination of move.e.t by the.brain＇s basal ganglia circuitry. This is e.ide.ce. by the.loss of the.e.ne.rons, re.ulting in the.cardinal motor de.icits associate. with parkinson＇s dise.se. In orde. to fully unde.stand the.physiology of the.e.ke. ne.rons and de.e.op pote.tial the.apie. for the.r loss, it is e.se.tial to de.e.mine.if and how dopamine.gic ne.rons are.re.le.ishe. in the.adult brain. Re.e.t work has pre.e.te. e.ide.ce.for adult ne.roge.e.is of the.e.ne.rons by Ne.tin＋/Sox2 ne.ral proge.itor ce.ls. We.sought to furthe. validate.this finding and e.plore.a pote.tial atypical origin for the.e.proge.itor ce.ls. Since.ne.ral proge.itor ce.ls have.a proximal association with the.vasculature.of the.brain and subse.s of e.dothe.ial ce.ls are.Ne.tin＋, we.hypothe.ize. that dopamine.gic ne.ral proge.itors might share.a common ce.l line.ge. The.e.ore. we.e.ploye. a Ve.cadhe.in promote.-drive. CRe.RT2：TIlox/Tlox transge.ic mouse.line.to ablate.the.tyrosine.hydroxylase.ge.e.from e.dothe.ial ce.ls in adult animals. Afte. 26 we.ks, but not 13 we.ks, following the.ge.e.ic blockade.of tyrosine.hydroxylase.e.pre.sion in Ve.cadhe.in＋ ce.ls, we.obse.ve. a significant re.uction in tyrosine.hydroxylase. ne.rons in the.substantia nigra. The.re.ults from this ge.e.ic line.ge.tracing study sugge.t that dopamine.gic ne.rons are.re.le.ishe. in adult mice.by a Ve.cadhe.in＋ proge.itor ce.l population pote.tially arising from an e.dothe.ial line.ge.

关键词： ne.ve.re.e.e.ation ne.ral proge.itor ce.ls adult ne.roge.e.is e.dothe.ial ce.ls substantia nigra dopamine.gic ne.rons parkinson's dise.se mouse.mode.