Prions: tlhaloso, sebopeho, mosebetsi, lefu, thibelo, ho felisa, phekolo, phetiso. (2023)

o na le li-prions?

• Li-prion ke liprotheine tse sa tloaelehang kapa tse sa phutholohang tse bakang mafu a bolaeang liphoofolong le bathong ka ho fetisetsa sebopeho sa tsona se sa phutholohang ka mokhoa o tloaelehileng oa protheine e tšoanang.
• Li-prion li baka mafu a sa phekoleheng, a bolaeang le a tšoaetsanoang a amanang le neurodegenerative ho batho le liphoofolo. Lefu lena, ho na le ho fokotseha butle-butle mosebetsing oa boko.
• Lentsoe lena le qalile ho qaptjoa ke setsebi sa methapo ea kutlo sa Amerika le setsebi sa biochemist Stanley Benjamin Prusiner ka 1982.PrionyLentsoe prion le tsoa ho "protheine e tšoaetsanoang ka karoloana".
• Li tšoaetsanoa ka tsela e fapaneng ka ho felletseng le libaktheria,Parasitele mafu a mang a tšoaetsanoang; ha ba na liphatsa tsa lefutso.
• Li-prion li entsoe ka protheine e bitsoang prion protein (PrP).
• Lefu lena ha lea tloaeleha hoo ho bang le bakuli ba bacha ba ka bang 350 selemo le selemo United States.
• Lefu lena, PrP e bokellana ka har'a lisele tsa boko 'me e qala ho bokellana' me e qala ho senya le ho bolaea lisele tsa methapo.
• E senya lisele tsa boko, e etsa masoba a manyenyane a shebahalang joaloka liponche ka tlas'a microscope.
• Nako ea ho kenngoa ha mafu a prion e tloha ho lilemo tse 5 ho isa ho tse 20.

Thepa ea Prion

1. Prion ratioVaerase'me e ka bonoa tlas'a microscope ea elektronike.
2. Li hlaha feela ka microscope ea elektronike ha li kopana ho theha sehlopha.
3. Li-prions ha li na nucleic acid. Ka hona, ba hanela mekhoa ea ho senya likokoana-hloko ka ho pshatla li-nucleic acid.
4. Li-prion ha li fe batho sesole sa 'mele hobane ke mefuta e sa tloaelehang ea liprotheine tse tloaelehileng.
5. Normal PrP e na le likhoele tse tenyetsehang tse bitsoang alpha helices, ha PrP e sa tloaelehang liheli tsena li otlolloa ho ba sebopeho se rarahaneng se bitsoang beta sheet.
6. PrP keE hanyetsana le proteases, mocheso, mahlaseli a ionizing le formaldehyde.
7. Ka 2011, bo-rasaense ba ile ba fumana hore li-prion li ka tsamaisoa ke likaroloana tse tsamaisoang ke moea tse kang li-aerosol.
8. Li-prions li ka silafatsoa ke proteolysis kapa ho fokotsa kapa ho senngoa ha sebopeho se phahameng sa protheine, se ka finyelloang ka sodium hypochlorite, sodium hydroxide le li-detergent tse matla tsa acidic tse kang LpH.
9. Bafuputsi hajoale ba ntse ba batlisisa ka ho hlaka ha ozone e le mokhoa o ka bang teng oa ho etsa denaturation le ho se sebetse.

Sebopeho sa Prion

Liprotheine tsa Prion li fumaneha hohle liphoofolong le bathong ba phetseng hantle. Ho na le mefuta e 'meli ea li-prions, tse kang:

• polystyrene,E nkoa e le mokhoa o tloaelehileng oa protheine. Mona C e bua ka "cellular" PrP. Protheine ena e hlophisitsoe hantle.
• praseodymium,Ke mofuta o tšoaetsanoang oa protheine ea prion. Sc mona e bua ka "scrapie", lefu la prion le fumanoang linkung. Protheine ena ke polydisperse mme e hlahisoa ka boemo bo batlang bo fokola.

polystyrene

• Ke protheine e atisang ho fumanoa liseleng tsa lisele.
• E na le li-amino acid tse 209 le bond ea disulfide.
• Boima ba molek'hule ke hoo e ka bang 35-36 kDa.
• E hlaha haholo-holo ka mekhoa ea α-helical.
• Ho na le mefuta e fapaneng ea protheine ena, mohlala, sebopeho sa sele se le seng se tšehetsoa ke glycolipids le ntho e le 'ngoe ea transmembrane.
• Protheine ena ha e na pula, ho bolelang hore e ke ke ea aroloa ka mekhoa ea centrifugation.
• Liprotheine tsena li tlama li-ion tsa koporo(II) ka kamano e phahameng.
• Enzyme ea proteinase K e ka sila protheine ea PrPc habonolo.
• Phosphoinositide phospholipase C (PI-PLC) e ntša protheine ena ka holim'a sele ka ho petsola ankora ea glycolipid ea glycophosphatidylinositol (GPI).
• Protheine e thusa ho bokella li-membrane tsa lisele, matšoao a intracellular 'meleng,' me e ka 'na ea ameha puisanong ea lisele tsa boko.

praseodymium

• Ena ke PrP kapa mofuta o monyenyane o tšoaetsanoang o bitsoang prions.
• Protheine ena e ka fetola protheine e tloaelehileng ea PrPc hore e be mofuta o sa tloaelehang oa tšoaetso ka ho fetola sebōpeho kapa sebopeho sa eona.
• Leha sebopeho sa 3D sa protheine ena se sa tsejoe, ho lumeloa hore se na le sebopeho sa leqephe la beta.

Phetoho ea pele kapa mokhoa oa ketso

Ho na le likhopolo tse peli mabapi le ho ikatisa ha protheine ea prion, mohlala:

1. mohlala heterodimeru

• Ona ke mohlala oa pele o hlalosang hore na protheine ea prion e ikatisa joang. Ho latela mohlala ona oa phetisetso, molek'hule e le 'ngoe ea PrPSc e hokahane le molek'hule e le 'ngoe ea PrPC, e ntan'o susumetsa phetoho ea PrPC ho PrPSc.
• Limolek'hule tse peli tsa PrPSc joale lia kopana 'me li ka fetoloa ho feta PrPC.

2. Mehlala ea likhoele

• Ho latela mohlala ona, PrPSc e sebetsa joalo ka li-fibrils.
• Karolo ea ho qetela ea fibril ena e tlama ho PrPC ebe e fetolela ho PrPSc.

Tloaelo e Tloaelehileng PrP

1. lefu la lisele tse laoloang

Ho na le liprotheine tse 'maloa tse kang prion' meleng ea rona, tse kang MAVS, RIP1, le RIP3. Protheine ena e bokellana ho filamentous amyloid fibrils mme e qala lefu la lisele tse laoloang.

2. memori ea nako e telele:E ts'ehetsa ho boloka mohopolo oa nako e telele.
3. Tsosoloso ea lisele tsa stem:Liphuputso tse entsoeng ke Whitehead Institute for Biomedical Research li bontšitse hore PrP e bohlokoa bakeng sa ho tsosolosoa ha masapo.
4. khanyetso:E sebetsa e le tšireletso ea tlhaho 'me e na le thepa ea antiviral khahlanong le likokoana-hloko tse ngata, ho kenyeletsa le HIV.

Mefuta ea mafu a prion

1. Mafu a batho ba prion

• Lefu Creutzfeldt-Jakob (CJD)
  • E boetse e tsejoa e le subacute spongiform encephalopathy kapa neurocognitive impairment e bakoang ke mafu a prion.
  • CJD ke lefu la boko le bolaeang le ileng la fumanoa ka lekhetlo la pele ka 1920.
  • Matšoao a lefu lena a kenyelletsa mathata a ho hopola, ho fetoha ha boitšoaro, ho se tsamaisane hantle, pono e lerootho, 'dementia', ho sisinyeha ka boithaopo, bofofu, bofokoli le koma.
  • Maemong a mangata, boloetse bona bo itlela feela, ’me maemong a seng makae bo futsitsoe ho motsoali.
  • Ha ho na pheko bakeng sa CJD.
  • Maemo a mangata a lefu lena a ama batho ba ka holimo ho lilemo tse 60.
  • Lefu lena le khetholloa e le transmissible spongiform encephalopathy.
  • CJD e ka fetisoa ka lisele tsa boko ba motho tse silafetseng, li-graft tsa corneal, li-graft tse kopanetsoeng kapa li-implants tsa electrode, le hormone ea kholo ea motho.
  • Ho na le mefuta e meraro ea CJD, joalo ka:ka linako tse ling (sCJD),Sena se bakoa ke ho senyeha ho sa tloaelehang ha protheine ea prion.Lelapa (fCJD),E etsahala ka phetoho e futsitsoeng ho prion protein gene.fumana CJD,Sena se ka etsahala ka ho kopana ka ho toba le lisele tse tšoaelitsoeng tsa motho ea tšoaelitsoeng.
• Matsoao ke Gerstmann-Straussler-Scheinker
  • Lefu la Gerstmann-Sträussler-Scheinker le ile la hlalosoa ka lekhetlo la pele ka 1936.
  • Ke lefu le sa tloaelehang, hangata la lelapa, le bolaeang la neurodegenerative.
  • Lefu lena le ama feela bakuli ba lilemo tse 20 ho isa ho tse 60.
  • E khetholloa e le transmissible spongiform encephalopathy (TSE).
  • Matšoao a kenyelletsa ataxia e tsoelang pele, matšoao a pyramidal, esita le 'dementia' ho batho ba baholo.
• ho hlobaela hoa bolaea
  • Ena ke boloetse bo sa tloaelehang bo bakang bothata ba ho robala 'me bo mpefala ha nako e ntse e ea.
  • Matšoao a mang a lefu lena a kenyelletsa mathata a puo, mathata a ho hokahanya, 'dementia' le lefu.
  • E etsahala ka liphetoho tsa lefutso tse kenyang protheine ea PrPC.
  • Ho na le mefuta e 'meli ea lefu lena, joalo kalefu la ho hlobaela (FFI)e leng autosomal e laolangNako le nako fatal insomnia (SFI)E bakoang ke phetoho ea liphatsa tsa lefutso.
  • Sena se ka fumanoa ka lithuto tsa boroko le PET scans.
• omme
  • Ke lefu le sa tloaelehang haholo, le sa phekoleheng le le bolaeang la neurodegenerative.
  • Lefu lena le hlaha ho batho ba Fore ba Papua New Guinea.
  • Ke lefu le tšoaetsanoang la spongiform encephalopathy (TSE).
  • Matšoao a kenyelletsa cerebellar ataxia e ntseng e tsoela pele kapa ho lahleheloa ke ts'ebelisano le taolo ea ho sisinyeha ha mesifa.
  • Lentsoe kuru ke selelekela sa kuria kapa guria ("ho falla"). Kúru ka boeona e bolela "ho thothomela".
  • Lefu lena le boetse le bitsoa "lefu la litšeho".
• Ho fapana le mafu a protease-sensitive prion
  • Lefu lena le boetse le tsejoa e le lefu la protease-sensitive prion.
  • Lefu lena le ama feela batho ba 2 kapa 3 ho batho ba limilione tse 100.
  • Matšoao a kenyelletsa ho senyeha ha puo (aphasia le/kapa dysarthria) le ho senyeha ho matla ha kelello le 'mele (dementia, ataxia, parkinsonism, psychosis, aphasia, le ho feto-fetoha ha maikutlo).
  • Lefu lena le ama batho ba ka holimo ho lilemo tse 70 feela.

O ka fumana malapa a spongiform encephalopathy, iatrogenic CJD (iCJD), variant CJD (vCJD), family CJD (fCJD), sporadic CJD (sCJD).

2. Prion mafu a liphoofolo

• scrapie
  • Ke lefu le bolaeang le le fokolisang le amang tsamaiso ea methapo ea linku le lipōli.
  • Ke lefu le tšoaetsanoang la spongiform encephalopathy (TSE).
  • Lefu lena ha le tšoaetse batho.
  • Matšoao a lefu lena a kenyelletsa melomo e otlang, ho hulanya maoto, ho rotha metsi ho feteletseng, le ho hohla boea majoeng, lifateng kapa terateng.
  • Tsela e atlehang ka ho fetisisa ea ho thibela ho ata ha scrapie ke ho arola le ho bolaea batho ba kulang.
• bovine spongiform encephalopathy
  • Lefu lena le boetse le tsejoa e le lefu la mad cow disease.
  • Ke lefu la neurodegenerative la likhomo.
  • Matšoao a lefu lena a kenyelletsa boitšoaro bo sa tloaelehang, bothata ba ho tsamaea le ho theola boima ba 'mele.
  • The incubation nako ea lefu lena ke lilemo tse 'nè ho isa ho tse hlano.
  • Lefu lena le ka fetisetsoa ho batho e le lefu la Creutzfeldt-Jakob (vCJD) ka ho ja lijo tse silafetseng.
• turtle spongiform encephalopathy
  • E boetse e tsejoa e le lefu la hlanya la likamele 'me le tšoana le lefu la mad cow.
  • Lefu lena le ama likamele.
• lefu le sa foleng la ho senya
  • E tsejoang hape e le lefu la zombie deer, ke lefu le tšoaetsanoang la spongiform encephalopathy (TSE).
  • Bolwetse joo bo ama dikgama, kgama ya mosela o mosweu, kgama e khibidu, sika, elk, caribou le elk.
  • Matšoao a mafu ana a kenyelletsa ho theola boima ba 'mele ka ho sa feleng le matšoao a kliniki a tsamaisanang le tšenyo ea boko e ntseng e mpefala ha nako e ntse e feta, hangata e lebisang lefung.
  • Lefu lena le ka tšoaetsoa ka ho ja boko, lesapo la mokokotlo, mahlo, spleen, tonsils, lymph nodes ea phoofolo e tšoaelitsoeng.

Mafu a mang a akarelletsa lefu la ho ruruha ha boko (spongiform encephalopathy) (leo ho sa tsejoeng hore le tšoaetsanoa) le amang limpshe. Exotic ungulate encephalopathy (EUE) e ama Nyala, Oryx, Greater Kudu. Feline spongiform encephalopathy (FSE) e ama likatse. Transmissible mink encephalopathy (TME) e ama li-mink.

Phetiso ea mafu a prion

Maloetse a Prion a ka fetisoa ke;

1. E amohetswe:Ha motho a kopane ka kotloloho le lijo kapa thepa ea bongaka e silafalitsoeng ke PrP. Haeba motho a ka kopana le moroto, mathe le maro a mang a ’mele a phoofolo e tšoaelitsoeng.
2. lefa:PrP e sa phutholohang e ka bakoa ke liphetoho tsa tatellano ea likhoutu tsa PrP.
3. nako:Liforomo tsa PrP tse fetiloeng ntle ho lebaka.

Matšoao a mafu a prion

• Ho hloka thahasello, ho ferekana le ho tepella maikutlo.
• Bothata ba ho nahana, ho hopola, le ho lekanya.
• pherekano kapa pherekano.
• Myoclonus kapa ho thothomela ha mesifa.
• Ataxia kapa tahlehelo ya kopano.
• Ho hlobaela kapa bothata ba ho robala.
• puo e kgutsunyane kapa e thellang
• ho se bone hantle kapa bofofu

Ho hlahlojoa ha mafu a prion

• Ho thata ho fumana lefu la Prion hobane matšoao a lona a tšoana le a mafu a mang a neurodegenerative. Ho hlahloba boko ke eona feela tsela ea ho netefatsa mafu a prion, empa mokhoa ona o ka etsoa feela ka mor'a lefu.
• Hona joale ho na le liteko tse 'maloa tse fumanehang ho hlahloba mafu a prion, a kang magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), electroencephalogram (EEG).

Phekolo ea mafu a prion

Ha ho na phekolo e sebetsang bakeng sa mafu a prion. Litsebi tsa baeloji li sebetsa ka thata ho fumana phekolo e sebetsang bakeng sa mafu a prion.

Thibelo ea mafu a Prion

• Se je likhomo tse tsoang linaheng tse nang le BSE.
• U se ke ua sebelisa boko ba khomo le lesapo la mokokotlo e le lijo.
• Haeba u le mokuli oa prion, u se ke ua fana ka litho tsa 'mele, mali, kaha mali ke mojari o motle oa li-prions.
• Qoba lisebelisoa tsa bongaka tse sa tsoa kopana le lisele tsa methapo ea bakuli ba nang le lefu la prion.
• Hona joale ha ho na mokhoa oa ho thibela lefutso kapa mefuta e sa tloaelehang ea mafu a prion.

thepa ea mokhatlo

Scrapie, e mong oa baemeli ba sehlopha, o itokiselitse ho tsamaea ka potlako ho litoeba le litoeba tse ling tse nyenyane, moo ho leng bonolo ho ithuta hobane o qeta nako e nyenyane le tsona. Tsebo e ngata mabapi le lintho tsa tlhaho le tsa 'mele tsa mahlahana ana e fumanoe lithutong tse entsoeng ka litoeba le li-hamster.

Ho fihla joale, liphuputso tse sebelisang boko ba kuru le boko ba CJD ha lia senola phapang ea mantlha ho tsoa ho mefuta ea scrapie ntle le meeli ea sehlopha se amohelang batho. Haufinyane tjena, mefuta e ikamahantseng le litoeba tsa kuru le CJD e se e fumaneha. Mokhoa o tšepahalang ka ho fetesisa o teng oa ho etsa tlhahlobo ea meriana ena ke bioassay ea ho qetela ea titration. Lithethefatsi tsena li thata ho ithuta ka lebaka la nako e telele ea ho lieha, e ka nkang lilemo tse fetang 5 lits'ebetsong tse ling.

bolulo ba mmele

• E ka sefa ho fihlela boholo ba pore ea 25-50 nm
• Mocheso o behiloe ho 90 ° C ka metsotso e 30, empa autoclaving e bolaea ka katleho. Leha ho le joalo, linyeoe tse ling tsa CJD li fetisoa ka lisebelisoa tsa autoclaved.
• Hydrophobic e nang le tšekamelo ea ho tlamella lintho tse tšoaetsanoang ho likarolo tsa cellular.
• Mefuta e fapana ka boholo ho tloha ho 40S ho isa ho 500S hammoho le latitudinal sucrose gradient.
• Boholo ba sepheo sa khetho ea mahlaseli a ionizing bo tloha ho 64,000 ho isa ho 150,000 daltons.
• Ho hloekisoa ha gel ka mor'a phekolo ea zwitterionic ho fane ka li-moles tse 50,000.
• Boima bo fapana pakeng tsa 1.08-1.30 g/ml

Litšobotsi tse ka holimo tsa 'mele li fana ka maikutlo a hore mofuta oa monomeric oa kokoana-hloko o ka ba o monyenyane, empa tlhokomelo e lokela ho nkoa. Bokhoni bo tsebahalang ba kokoana-hloko ea ho ipokella bo ka ’na ba nyenyefatsa liphello tsa lithuto tse sebelisang mahlaseli ho e kenya tšebetsong.

boikemelo ba mmele

• e hanyetsanang kapa e hlokang thuso ka tsela e itsengLi-aldehyde le metsoako e amanang le eona (formaldehyde, valeraldehyde, B-propiolactone), nucleases (ribonuclease, deoxyribonuclease), mocheso (80oC), mahlaseli a ultraviolet le ionizing, li-solvents tse bonolo (ethanol, xylene), li-non-ionic le tse seng tsa anionic.
• Ka mokhoa o itekanetseng IDiethyl ether, acetone, ethylene oxide
• e sa sebetseng hantleAutoclaved (134oC, e 15), proteases (pronase, trypsin, proteinase K), denaturing detergent (SDS), lithium ion tse matla tsa chaotropic (thiocyanate, trichloroacetate). Lithium tse matla solvents (phenol, chloroform, 2-chloroethanol), lithium oxidants (periodate, hypochlorite, permanganate), urea, sodium hydroxide.
• Le hoja li sa khone ho bolaea likokoanyana tse ngata, li mamella mekhoa e sa tšoaneng e sebelisoang ho thibela le ho bolaea likokoana-hloko.

lintho tse tloaelehileng tsa baeloji

• E ea tlhotla ebile e bonolo ho titrate.
• Ho ikatisa ho hoholo (ho fihla ho 108-1010 likarolo tse tšoaetsanoang / gram ea boko)
• E qala ho ikatisa ka lymph nodes, spleen le thymus. Ebe ka bokong. Bopaki ba tšoaetso ea kokoana-hloko ka tsamaiso ea methapo le ho tloha spleen ho ea sefuba ka methapo ea autonomic.
• Litšitiso tsa moamoheli le ho ikamahanya le maemo ho baamoheli ba bacha
• Liphapang tsa khatello (tse khethiloeng ke boits'oaro bo ikhethileng, latency le boemo ba tšenyo ea boko, le bokhoni ba ho theha li-amyloid plaques le bokhoni ba ho khetha li-isolates tse fapaneng (vaerase ea liphoofolo tse hlaha)
• Taolo ea liphatsa tsa lefutso tse amohelang batho e ama ho ba bonolo le ho hanyetsa.
• Tšitiso lipakeng tsa mefuta e ntseng e ikatisa butle le ka potlako
• Tloaelo ea lithane ha e khone ho ikatisa hampe.
• Karolo ea bohlokoa ea liprotheine ho ikatisa (mohlala, tšilo ea protease; phetoho ea lik'hemik'hale ka diethyl pyrocarbonate, diacetyl; ho se sebetse ka li-detergents tse kang SDS; ion inactivation le guanidine, thiocyanate, trichloroacetic acid; degeneration ea urea le phenol)

tlhaello ea lintho tse phelang

• nako e telele ea ho incubation
• boits'ireletso kapa boits'ireletso ba mmele
• Lefu le sa foleng le sa ipheteng kapa le sa ipheteng
• Ho kenyelletsa liphetoho tsa spongy le nts'etsopele ea tahlehelo ea neuronal le gliosis
• EMR Ha e na likaroloana tsa vaerase
• Nucleic acid e mahareng le ho hanyetsa lits'ebetso tsa inhibitory tsa nucleic acid joalo ka pH e tlase, li-nuclease, mahlaseli a UV ho 237 nm, zinki hydrolysis, hydroxylamine activation le psoralen.
• Li-immunosuppressants, li-immune booster kapa li-antiviral. Splenectomy e ka ama nts'etsopele ea ts'oaetso.
• Ha ho CPE moetlong oa lisele
• Mefuta e sa tloaelehang ea ho hanyetsa lik'hemik'hale tse itseng le phekolo ea 'mele
• Ho kenngoa ha li-amyloid-associated fibrils / scratie le phetoho ea protease-sensitive protheine (PrP) e tloaelehileng ea protease-resistant homologue.

Nako e telele ea ho qhoqhoa ha likokoana-hloko tsena e ba khetholla ho mafu a mang a kokoana-hloko. Li bonahala li ikatisa ka lebelo le tsitsitseng ka mor'a ho entoa. Ha ba se ba na le phihlello ea CNS mme ba fihla boima bo boima, ba hlaha tleliniking. Ho haella ha karabelo ea 'mele ea ho itšireletsa mafung ke sephiri, empa ho ka hlalosoa ka monyetla oa hore protheine ea moeti e fetotsoeng e ka ba sesosa.

Bopaki bo fana ka maikutlo a hore PrP e fetotsoeng e bohlokoa, empa hase eona feela motsoako oa moriana. Ha ho hlake hore na ho na le karolo ea nucleic acid. Lintho tse ling tsa 'mele li fana ka maikutlo a hore NA ha se ntlha ea bohlokoa tšoaetsong, joalo ka ho hanyetsa li-protease, mahlaseli a UV ho 237 nm, zinki hydrolysis le ho thibela photochemical inhibition ka psoralen le lik'hemik'hale tsa lik'hemik'hale tse nang le hydroxylamine.

Leha ho le joalo, livaerase tse ling tse tsebahalang li na le tse ling kapa litšobotsi tsena kaofela. Kamoo ho bonahalang kateng NA genome e nyane haholo (e ka tlase ho metheo ea 30) 'me ha e khone ho ba le protheine ea PrP.

Likhopolo tsa thepa ea Prion

Ho na le likhopolo tse peli tse kholo tse hlalosang thepa ea li-prions

Khopolo-taba ea protheine feela.

Li-prion li entsoe ka thepa ea protheine e ka menang ka litsela tse sa tšoaneng tse sa bonahaleng. Bonyane ka linako tse ling e fetisetsa liprotheine tse ling tsa prion tse bakang mafu ka mokhoa o ts'oanang le ho ata ha tšoaetso ea kokoana-hloko. Sehlahisoa sa mantlha sa phetolelo ea PrPC se tlameha ho fetoleloa ho mofuta o fetotsoeng ka har'a lisele tse nang le tšoaetso ea PrPSc. Phetoho ena e ka hlahisoa ke PrPSc (autocatalysis). Scrapie e 'ngoe le e' ngoe e khetholloa ke mofuta o fapaneng oa PrPSc o fetolang selelekela sa pele ho hlahisa ntho e tšoanang le eona. Liphapang tsa lefutso la PrPSc li ka hlalosa mofuta oa phetoho kamora ho fetisetsoa ho moamoheli e mong.

Haholo-holo, phetoho ea PrPC ho PrPSc e ka hlahisoa ke "invertase" encoding PrPSc. Mefuta e fapaneng ea scrapie e ka hlalosoa ke palo ea li-enzyme tse fapaneng, e 'ngoe le e' ngoe e sebelisoa ke mofuta o tšoanang oa PrPSc.

Khopolo-taba ea "nucleoprotein kapa virus".

Li-prions li entsoe ka li-nucleic acid tse nyane le li-protein codes. Mefuta e fapaneng e amana le mefuta ea nucleic acid e tšoanang le DNA ea kokoana-hloko.

Hona joale ho na le bopaki bo bongata bo tšehetsang khopolo ena ea "protheine feela". Malapeng a mabeli ao ho bonahalang a sa amana, le leng le tsoa United States le le leng la United Kingdom, Prusiner et al. Mofuta oa ataxic oa lefu la Gerstmann-Straussler o fumanoe o amana le phetoho ea codon 102 ea e 'ngoe ea PrP alleles, ho tloha ortho ho ea leucine. Liphetoho ha li so fumanehe ho batho ba phetseng hantle kapa ho bakuli ba nang le mefuta e meng ea li-prions tse sa tloaelehang kapa tse fumanoeng. Ho nahanoa hore liphetoho tsa liphatsa tsa lefutso li phetha karolo e itseng sesosa sa lefu lena. Maemong a nakoana a GSS le CJD, liphetoho tsa somatic li ka fana ka monyetla o moholo oa liphetoho tsa PrP PrPGSS kapa PrPCJD. PrPSc e kanna ea ba pathogenic ho bakuli bana, empa sena ke seoelo. Monyetla o mong ke hore li eketsa haholo ts'oaetso ea "'nete" ea ts'oaetso. Liphetoho tse ling tsa mofuta oa PrP li ka fumanoa malapeng a nang le CJD kapa GSS.

Li-scrapie prions, tse atisang ho nkoa ke li-hamster ebe li kenngoa ka har'a litoeba, li ne li e-na le nako ea ho incubation bonyane matsatsi a 500, e ileng ea fokotseha ho ea ho matsatsi a 140 nakong ea phekolo e latelang ea litoeba 'me ea lula e sa fetohe. Tatelano e tšoanang ea liketsahalo e ka bonoa ho hamster. Tabeng ea hamsters, "nucleoprotein theory" e hlalosa phapang ena ka phetoho ea boholo-holo le khetho. Leha ho le joalo, khopolo-taba ea liprotheine feela e fana ka maikutlo a hore phetoho ea PrPC ea moeti ho PrPSc e khelohileng, e ikhethang hase ketsahalo e tloaelehileng, empa ha e etsahala 'me e sa tsoa thehoa PrPSc ke, mofuta oa moamoheli o khona ho etsa liphetoho tse ling ka katleho le ka katleho. Kapele.

Prusiner et al. Litoeba tse hlalosang mofuta oa hamster oa PrP li entsoe. Ba ile ba li enta ka li-prions tse entsoeng ka li-hamster. Liphello li ne li makatsa ha nako ea latency e khutsufalitsoe ho tloha matsatsing a fetang 500 (litoeba tsa taolo) ho ea matsatsing a 75 ho litoeba tse sa fetoheng. Tšoaetso ea Prion ho litoeba e fokotsehile ka tsela e tšoanang. Litoeba tse tšoaelitsoeng ke hamster prions li ile tsa hlahisa li-prion tse neng li tšoaetsanoa ho hamster empa eseng litoeba. Leha ho le joalo, litoeba tsa transgenic tse tšoaelitsoeng ke li-prion tse entsoeng ke mouse li ile tsa hlahisa li-prion tse neng li tšoaetsanoa ho litoeba empa eseng ho li-hamster. Liphetho tsena li fana ka maikutlo a hore li-prions tse nkiloeng ho hamster li fetolela transgenic hamster PrPC empa eseng endogenous mouse PrPC ho PrPSc. Phapano lipakeng tsa mofuta ona e kanna ea amana le khaello ea ts'ebetso ea PrPC bakeng sa phetoho ka PrPSc e fapaneng.

Mofuta oa murine o hlalosang GSS proline ho phetoho ea leucine e ile ea kenngoa ho litoeba. Mothehi e motona le bana ba 34 ba transgenic ba ile ba hlahisa matšoao a methapo pakeng tsa libeke tse 7 le 39 mme ba shoa qetellong ea khoeli. Boko bo ile ba bontša maqeba a mangata a spongy, empa ho makatsang ke hore ha ho PrPSc e ileng ea bonoa ho sa tsotellehe matšoao a makatsang. Litoeba tse hlahisang hamster PrPC kapa PrPC e tloaelehileng ea mouse ha ea ka ea ba le matšoao. Litlhahlobo tsa boko ba litoeba li bontšitse tšenyo tsamaisong ea methapo e bohareng ho tse 'maloa tsa ente. Ka khopolo, thuto ena e fana ka maikutlo a hore liphetoho tsa PrP li ka lebisa ho GSS le CJD ea lelapa.

Kahoo, bopaki bo tšehetsa khopolo-taba ea protheine feela. Lebaka le ka sehloohong leo ka lona khopolo ena e nkoang e tšoenyehile ke ho ba teng ha mefuta e fapaneng ea li-prion. Ho na le mefuta e 'meli e fapaneng ea li-prions tsa mouse (tse fapaneng ka nako ea ho incubation), e' ngoe le e 'ngoe ea tsona e ka se shoe ka mofuta o le mong oa mouse, le hoja ho na le mofuta o le mong feela oa PrP. Litoeba li homozygous bakeng sa lefutso lena. Mefuta e fapaneng ea scrapie e khethiloe. Sena se bolela hore PrPC e tlameha ho fetoha litlhophiso tse ngata tse fapaneng joalo ka li-prions. Ho latela liphuputso tsena tse ncha, ho ka fihleloa ka mokhoa o sa tsitsang hore protheine ea PrP e phetha karolo ea bohlokoa ho pathogenesis ea spongiform encephalopathies. Hape ho ka etsahala hore protheine ea PrP e fetotsoeng e ikarabella bonyane ho tse ling kapa likarolo tsohle tse bakang tšoaetso.

Phuputso ea 2015 e fumane hore multiple system atrophy (MSA), lefu le sa tloaelehang haholo la neurodegenerative ea motho, le bakoa ke ho senyeha ha protheine e bitsoang alpha-synuclein. Ka hona, e boetse e hlalosoa e le lefu la prion.

E bale hape

• Bofofu bosiu ke eng | Matšoao | Contraindications | Mefuta | Lisosa

Ho phaella ho li-prion liphoofolong le bathong, li boetse li fumanoa ho li-fungus. Li-mushroom tsena li re thusa ho utloisisa li-prion tsa mammalian. Li-fungal prions ha li bake lefu la 'mele.