Prion Protein: Cov Molecule Ntawm Ntau Daim Ntawv Thiab Lub ntsej muag Part 3
Sep 05, 2024
Raws li kev txiav txim siab oligomer binding domains, cov kws tshawb fawb tau tsim cov tswv yim kho mob rau AD raws li hluavtaws peptides [204,223] thiab functionalA oligomer-binding compounds [149].
Nyem paub txoj hauv kev los txhim kho lub hlwb
Nyob rau hauv xyoo tas los no, ntau thiab ntau cov kev tshawb fawb tau pom tias muaj kev sib raug zoo ntawm oligomer khi thiab nco. Yog li dab tsi yog oligomer khi? Oligomers tuaj yeem nkag siab tias yog cov qauv polymer tsim los ntawm kev sib xyaw ua ke ntawm ib qho me me ntawm monomer molecules, uas feem ntau pom nyob rau hauv cov txheej txheem ntawm kev ua tiav ntau yam kev ua neej nyob hauv cov kab mob. Oligomer binding yog hais txog kev sib khi tshwm sim ntawm cov molecules. Daim ntawv ntawm kev khi no suav nrog tsis tsuas yog lub cev yam xws li cov khoom siv tshuaj lom neeg thiab cov teebmeem electrostatic tab sis kuj tseem muaj kev sib txuas ntawm cov molecules thiab kev sib cuam tshuam ntawm monomers.
Cov kev tshawb fawb tau pom tias kev sib raug zoo ntawm oligomer khi thiab kev nco yog nyob ze heev. Cov kws tshawb fawb tau pom tias thaum tib neeg nyuam qhuav kawm paub txog kev paub tshiab lossis kev txawj ntse, qhov kev paub no feem ntau tsuas muaj nyob hauv lub hlwb nco txog lub sijhawm luv thiab yooj yim tsis nco qab. Txawm li cas los xij, dhau sijhawm, qhov kev paub no yuav raug xa mus los ntawm lub sijhawm luv luv mus rau lub sijhawm ntev nco, kom nws ruaj khov rau hauv tib neeg lub hlwb. Hauv cov txheej txheem no, oligomer binding plays lub luag haujlwm tseem ceeb.
Tshwj xeeb, oligomer binding pab ntxiv dag zog rau lub koom haum thiab kev nco txog cov kev paub tshiab thiab kev txawj ntse hauv lub hlwb los ntawm cov txheej txheem nyuaj, suav nrog kev txhim kho neurotransmitter tso tawm, txhim kho kev ruaj ntseg ntawm cov paj hlwb, thiab txhim kho kev sib txuas ntawm neurons. Nyob rau tib lub sijhawm, nws tseem tuaj yeem cuam tshuam qhov tsis nco qab lub sijhawm luv luv, yog li ua kom lub cim xeeb ntev ntawm kev paub thiab kev txawj ntse.
Yog li ntawd, peb tuaj yeem txiav txim siab tias oligomer khi tuaj yeem txhawb nqa thiab ntxiv dag zog rau tib neeg kev nco, pab cob qhia thiab kawm paub tshiab thiab kev txawj ntse, thiab pab tiv thaiv kev nco tsis txhob maj ploj mus thiab poob qis. Txhawm rau tiv thaiv peb lub hlwb kev noj qab haus huv, peb yuav tsum ua ntau yam kev tawm dag zog thiab kev coj ua, xws li kev kawm cov txuj ci tshiab, mloog suab paj nruag, thiab kev tawm dag zog, los txhawb oligomer khi thiab ntxiv dag zog rau lub hlwb. Ua li no, peb lub hlwb tuaj yeem noj qab haus huv thiab muaj zog, muaj zog thiab muaj zog. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche tuaj yeem txhim kho kev nco zoo vim Cistanche muaj cov tshuaj tiv thaiv antioxidant, tiv thaiv kev laus, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidative thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv. paj hlwb. Tsis tas li ntawd, Cistanche tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm muaj peev xwm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv qhov tshwm sim ntawm kev paub tsis meej thiab cov kab mob neurodegenerative.
Cov tsim hluavtaws peptides tau pom tias txo qis tus nqi pib ntawm A fibrillization, inhibit txoj kev sib sau ua ke ntawm A byreducing A oligomer uptake, thiab tiv thaiv kab lis kev cai hippocampal neurons los ntawm oligomer-induced retraction ntawm neurites thiab poob ntawm cell membrane kev ncaj ncees [204] whereas D -peptideRD2D3 muaj kev vam meej hauv kev cuam tshuam nrog PrPC-A oligomer assemblyand tau raug pom zoo ua tus neeg sawv cev kho mob zoo hauv AD [223].
7. Cov lus xaus
Cov kev tshawb fawb soj ntsuam txhawb qhov tseeb tias prion protein thiab / lossis prion protein fragments koom nrog hauv myelin homeostasis, ischemia, thiab neurodegeneration uas lawv tuaj yeem ua haujlwm sib txawv (Daim duab 2).
Raws li cov ntaub ntawv tam sim no, anchoredPrP thiab / lossis cov khoom tawg (N1, shed PrP) cuam tshuam nrog Adgrg6 los tswj peripheralnerve myelin homeostasis.
Txawm hais tias tau sim txuas PrP mus rau lwm qhov Adgrg6- cov txheej txheem kho kom haum, tsis muaj kev koom tes ncaj qha tau pom. Hauv kev mob stroke, qhov kev nthuav qhia ntawm PrP yog upregulated.
Anchored PrP koom nrog hauv kev sib kho cov teeb liab txoj hauv kev los ntawm transmembrane thiab cytosolic receptor proteins. Txawm hais tias xav tau kev kawm ntxiv, cov ntawv tso tawm tuaj yeem ua lub luag haujlwm txiav txim siab hauv neuroprotection thiab rov tsim dua tshiab, suav nrog kev tswj hwm kev sib cuam tshuam ntawm microglia thiab hlwb hlwb thiab kev txhawb nqa ntawm neurogenesis.
EVs thiab SUVs muaj kev nplua nuj nyob rau hauv PrP fragments tej zaum yuav yog ib qho tseem ceeb xa mechanisms hauv neuroprotection thiab neurodegeneration; kev tshawb fawb ntxiv yog xav tau los ua pov thawj lawv lub luag haujlwm.
Hauv cov kab mob neurodegenerative, anchored PrP ua raws li receptor rauA oligomers, -syn oligomers, thiab tau aggregates thiab tuaj yeem kho oligomer-inducedcytotoxicity. Lub ntsiab lus ntawm kev sib cuam tshuam ntawm oligomer thiab PrP tej zaum yuav yog qhov chaw txaus nyiam rau kev txhim kho tshuaj tab sis kev kho kuj tseem muaj xws li kev tswj hwm ntawm lwm tus neeg koom tes hauv cov txheej txheem no.
Sib cav lawv lub luag haujlwm tiv thaiv, tso tawm PrP tawg tuaj yeem khi cov tshuaj oligomers thiab pab kom lawv depletion. Kev txhawb nqa lub luag haujlwm no, los ntawm PrP tau pom tias khi PrPSc thiab A oligomers hauv amyloid plaques, uas tej zaum yuav muaj tshuaj lom tsawg dua li oligomers.
Txhawm rau xaus, ntau qhov qhia tau hais tias prion protein thiab prion protein fragments tej zaum yuav muaj ntau yam (qee zaum txawm intertwined) lub luag hauj lwm hauv strokes thiab neurodegeneration. Yuav kom paub meej lawv lub luag haujlwm hauv cov txheej txheem no, yuav tsum muaj kev tshawb fawb ntxiv hauv cov haujlwm no.
Daim duab 2. Proteins, kev taw qhia txoj hauv kev, thiab kev sib cuam tshuam uas yuav cuam tshuam los ntawm PrP thiab / lossis PrPfragments. Cov txheej txheem no nthuav tawm ntau yam proteins, qhia txoj hauv kev, thiab kev sib cuam tshuam uas tau tshaj tawm txog PrP thiab / lossis nws cov khoom tawg.
Hauv ischemic stroke, PrP hom tau pom tias muaj kev koom tes hauv kev hloov kho neuroprotection, neurite outgrowth, neurogenesis, thiab angiogenesis. Hauv cov kab mob neurodegenerative, tso tawm PrP fragments tuaj yeem tiv thaiv qhov cuam tshuam ntawm PrP regulatesoligomer-induced toxicity.
PrP thiab nws cov derivatives kuj koom nrog hauv Adgrg6-induced myelinationhomeostasis (txiv kab ntxwv) thiab tej zaum yuav koom nrog microglia kev sib txuas lus thiab kev sib txawv nrog rau kev tswj cov kev sib txuas lus hauv nruab nrab los ntawm EVs thiab SUVs, thiab lwm yam.
Ntau qhov kev sib tham sib tham tau tswj hwm los ntawm kev sib cuam tshuam ncaj qha nrog PrP hom thaum lwm tus raug tswj tsis ncaj. Txoj kev tiv thaiv thiab kev sib cuam tshuam yog xim xiav thaum xim ntsuab nthuav tawm cov txiaj ntsig tsis zoo.
Tus Sau Kev Koom Tes: VK tau tsim cov ntawv sau thiab sau thawj tsab ntawv; VCŠ. ˇconceptualized cov ntawv sau Scope thiab critically tshuaj xyuas cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Cov Nyiaj Txiag: Cov haujlwm no tau txais nyiaj los ntawm Slovenian Research Agency (ARRS tus lej nyiaj P4-0176).
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
Cov ntaub ntawv
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