Structural And Functional Insights Rau -Synuclein Fibril Polymorphism Part 4
May 20, 2024
7. Phase Separation thiab Nucleation: Molecular Basis ntawm Fibril Polymorphism
Tsis ntev tom qab qhov kev tshawb pom tias -Syn aggregation tsis yog txuas rau PD nkaus xwb tab sis kuj MSA thiab DLB, thaj chaw tshawb fawb tseem ceeb tau tsom mus rau kev nkag siab txog lub peev xwm ntawm cov protein ua rau kev kho mob thiab kab mob sib txawv neurodegenerative.
Thaum koj loj tuaj, koj yuav pom tias koj lub cim xeeb tsis zoo li thaum koj tseem yog menyuam yaus. Qee zaum koj yuav xav tias koj lub hlwb "rusty" thiab nws nyuaj rau nco ntsoov cov ntaub ntawv tshiab. Tab sis dab tsi tuaj yeem ua tau los txhim kho qhov xwm txheej no? Kev tshawb fawb nyob rau xyoo tas los no tau pom tias muaj kev sib raug zoo ntawm MSA (dopamine-saccharide complex) thiab nco.
MSA yog lub neural circuit uas muaj cov neurotransmitter dopamine. Dopamine yog ib qho tseem ceeb neurotransmitter hauv lub hlwb thiab muaj feem xyuam nrog kev xav, kev txhawb siab, thiab kev txav. Sunstones yog nuclei nyob rau hauv lub hlwb uas tswj kev txav thiab sib koom tes. Kev sib raug zoo nrog dopamine yog tias thaum lub cev basal yog txhawb los ntawm dopamine, nws yuav ua rau kom muaj kev sib txuas ntawm lub hlwb neurons, yog li txhawb kev tsim thiab kev sib koom ua ke ntawm kev nco.
Kev tshawb fawb qhia tau tias MSA tuaj yeem qhib thiab txhawb nqa los ntawm kev ua si digital, kev cob qhia suab paj nruag, kev tawm dag zog lub cev, thiab kev sib raug zoo. Cov qauv no tuaj yeem ntxiv dag zog rau kev sib txuas rau cov kua cerebrospinal los ntawm kev tso tawm dopamine. Piv txwv li, kev tawm dag zog lub hlwb zoo li qub, xws li Sudoku thiab cov lus sib dhos sib dhos, tau pom los txhim kho kev nco. Kev cob qhia suab paj nruag kuj tau pom los txhawb MSA circuits thiab txhim kho lub peev xwm nco. Tsis tas li ntawd, kev tawm dag zog lub cev thiab kev sib raug zoo hauv zej zog kuj tau pom tias muaj kev cuam tshuam zoo rau kev ua kom MSA, yog li txhawb lub hlwb kev noj qab haus huv thiab kev nco txhim kho.
Hauv cov ntsiab lus, txij li MSA cov dej num muaj txiaj ntsig zoo rau kev nco, nrhiav thiab koom nrog cov haujlwm uas txhawb nqa MSA yog ib kauj ruam tseem ceeb hauv kev txhim kho kev nco. Ua lub cev ua haujlwm, koom nrog hauv kev ua ub no, thiab kawm cov txuj ci tshiab tuaj yeem qhib thiab txhawb nqa MSA Circuit Court, yog li txhawb kev txhim kho lub hlwb thiab kev nco. Cia peb pib txij tam sim no mus thiab koom tes nrog cov dej num no txhawm rau txhaj cov zog tshiab thiab muaj zog rau hauv peb lub hlwb. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv ntau yam.
Nyem paub txoj hauv kev los txhim kho lub hlwb
Ob peb xyoos dhau los, prion strain hypothesis tau tshwm sim los ua qhov kev piav qhia rau kev pom muaj kab mob sib txawv hauv synucleinopathies. Txawm hais tias muaj ntau yam ntawm biophysicaland biological cov ntaub ntawv txhawb nqa lub hav zoov ntawm -Syn hom [29,30,32–35,53], nws tseem tsis tau paub meej tias cov kab mob no tshwm sim thiab cov yam ntxwv uas ua rau lawv tsim hauv vivo.
Cov lus teb tej zaum yuav dag nyob rau hauv delineating lub aggregation pathways thiab discerning lub moleculardrivers nyob rau hauv lub hauv paus strain formation.Amyloid tsim tsis tsuas yog tswj hwm los ntawm lub hauv paus nucleation tab sis yog dominated los ntawm theem nrab nucleation txheej xwm los ntawm feem ntau ntawm cov aggregation loj hlob theem, asdiscussed ua ntej [189].
Qhov thib ob nucleation no suav nrog qhov elongation ntawm cov fibrils tshiab los ntawm cov noob uas twb muaj lawm los ntawm kev nrhiav cov monomers los ntawm kev daws. Ib qho kev hloov pauv hauv kev daws teeb meem ntawm cov fibrils zoo li hloov pauv tus nqi ntawm thawj thiab theem nrab nucleationevents [188,189]. Piv txwv li, acidic pH txhim khu kev khi ntawm -Syn monomers mus rau lub fibril nto, yog li ua rau cov theem nrab nucleation tus nqi [189,302].
Txij li thaum cov noob tau nthuav tawm ntawm cov aggregates yog ntaus nqi los ntawm kev tawg thiab elongation offibril noob, qhov no ua rau peb xav tias qhov tshwm sim ntawm cov kab mob yog, yam tsawg kawg hauv ib feem, qhov tshwm sim ntawm cov nucleation theem nrab. Ntxiv mus, ntau hom kev sib koom ua ke ntawm ntau theem ntawm kev sib sau ua ke kinetics [17,303,304], qhia txog kev koom tes ntawm aggregationintermediates hauv dictating polymorphism.
Daim duab qhia ntawm qhov chaw conformational ntawm -Syn monomer qhia txog cov txheej txheem subpopulation ntawm -Syn monomer uas txhawb nqa nws txoj kev sib txuas nrog daim nyias nyias thiab induces tsim ntawm ntau yam oligomers thiab fibrils [170].
Peb lub chaw kuaj mob tsis ntev los no tau pom tias qhov sib txawv ntawm cov nucleation thaum lub sij hawm sib sau ua ke ua lub hauv paus ntawm keeb kwm ntawm polymorphism [252]. Peb tsim ob lub polymorphs sib txawv, HMFs (Helix matured fibrils) thiab PMFs (Pre-matured fibrils), los ntawm kev sib sau ua ke uas tsim los ntawm tib lub rooj sib txoos.
PMFs tsis muaj qhov ruaj khov amyloid core thiab muaj random coil cov ntsiab lus nrog rau -cov ntsiab lus. Ntxiv mus, cov txheej txheem -daim ntawv los ntawm residues 74-79 yog tsis tuaj ntawm nws cov NAC domain ( residues 65-80), qhia PMFs kom tsawg dua fibril. hom. Ntawm qhov tsis sib xws, morphologically thiab structurally txawv HMFs yog ntau compact thiab zoo-ordered nrog ib tug stabilityfibril core [252].
Cov no muaj ntau qhov chaw hydrophobic thiab muaj peev xwm muaj tshuaj lom ntau dua li PMFs tsawg dua. Cov polymorphs no tsis tsuas yog muaj qhov sib txawv ntawm cov qauv, tab sis kuj nthuav tawm cov haujlwm lom neeg sib txawv [252].
Ib txoj kev tshawb fawb zoo sib xws nrog rau kev txheeb xyuas qhov sib xyaw nruab nrab ntawm cov phospholipid membrane qhia tias prefibrillar hom muaj ob lub voj voog nrog cov seem 57 txog 61 thiab 71 txog 80 [305]. Cov intermediates tom qab ntawd hloov mus rau hom fibrillar nrog feem ntau ntawm thaj av NAC thiab N-terminus (residues 38-80) ua ib feem ntawm qhov kawg fibrilconformation [305].
Cov kev tshawb fawb kuj tau tshaj tawm nrog kev sib sau ntawm A , PrP, thiab tau, qhov chaw sib txawv ntawm cov khoom siv roj ntsha emanate vim qhov sib txawv ntawm cov polymorphs [28,306-309]. Piv txwv li, morphologically thiab structurally sib txawv A fibrilsformed nyob rau hauv quiescent thiab agitating tej yam kev mob qhia qhov sib txawv tseem ceeb nyob rau hauv toxicity inprimary neurons, nrog quiescent fibrils muaj tshuaj lom ntau dua piv rau lwm tus [28].
Kev sib txawv ntawm cov qauv sib txawv PrPSc conformations nthuav tawm cov tswv tsev ntawm tes tropism, nrog rau cov kab mob tshwj xeeb nyiam tsom rau cov neurons, astrocytes, lossis txawm tias ob qho tib si [307,308].Yog li, -Syn hom uas tshwm sim los ntawm heterogeneous nucleation nyob rau hauv aggregationpathway yuav ua rau kev kho mob thiab pathological. los ntawm kev nthuav tawm variablecytotoxicity thiab txawv prion zoo li cov khoom (Daim duab 5).
Tsis ntev los no, kev hloov pauv ntawm lub tswv yim ntawm kev sib sau ua ke ntawm cov protein mus rau qhov tseem ceeb tshaj plaws, uas yog kua-kua theem sib cais (LLPS), tau cuam tshuam rau thaj chaw thiab tau coj cov kev tshawb fawb hauv kev coj tshiab [310-314]. Proteins yog incubatedin ntau yam xwm txheej, piv txwv li, pH, kub, thiab ntsev tej yam kev mob [315–317].
Cov txheej xwm sib cais ntawm Thephase tau txhawb nqa nyob rau hauv lub xub ntiag ntawm molecular neeg coob coob, xws li polyethylene glycol, dextran, los yog ficoll, uas pab ua kom cov protein ntau hauv zos thiab ua kom lub cev muaj zog [315–318]. Tom qab ntawd, qhov dynamicity, maturation, thiab aggregation profile raug soj ntsuam siv ib tug tshwj xeeb ua ke ntawm biophysical, biochemical, thiab spectroscopic txoj kev [315,317].
Cov phenomena ntawm theem sib cais ntawm ntau yam amyloidogenic proteins tau tshwm sim ua ntej aggregation thiab fibril tsim. Nws tau raug pom zoo tias qhov muaj qhov tsis sib haum xeeb hauv cheeb tsam (IDRs), prion-zoo li domains (PLD), thiab cov tsis muaj qhov nyuaj (LCD) txhawb kev tsim cov theem sib cais condensates ntawm amyloidogenicproteins [310,315,316,319,320].
Peb lub chaw kuaj mob tsis ntev los no tau pom tias LLPS ntawm -Syn yog qhov tshwm sim tseem ceeb nyob rau theem pib lag luam thiab ua ntej nws cov kev sib sau ua ke raws li theem sib cais (muaj neeg coob coob, kev ntxhov siab, amyloid co-factors, thiab lwm yam) [315].
Cov tsos mob ntawm cov theem sib cais cov tee dej nyob rau hauv lub lag luam theem ntawm aggregation kinetics qhia tias LLPs tuaj yeem txhim kho cov xwm txheej nucleation los ntawm kev nce hauv zos concentration ntawm cov protein molecules [315,320]. Ntxiv mus, cov theem-sib cais -Syn droplets undergoliquid-rau-khoom hloov nrog lub sij hawm thiab tshwm sim nyob rau hauv tsim ntawm amyloid hydrogel [315].
Cov amyloid hydrogels tau pom yav dhau los rau kev nkag mus rau cytotoxic oligomers andfibrils [321], qhia tias muaj peev xwm ua fibrils tsim los ntawm LLPS tuaj yeem ua rau muaj tshuaj lom. Txawm li cas los xij, nyob rau hauv ib txwm muaj kev sib koom ua ke (tsis muaj theem sib cais), -Syn fibrils qhia me me lossis tsis muaj cytotoxicity [322,323]. Qhov no qhia tau hais tias cov fibrils tsim nyob rau hauv theem-sib cais thiab tsis-theem-separating tej yam kev mob yuav txawv.
Ntxiv mus, cov fibril formationin dilute cov kev daws teeb meem (paub tias tshwm sim ntawm thawj thiab theem nrab nucleation) [189] thiab nyob rau hauv cov condensates (ntawm LLPS) tsis yog kev sib koom ua ke [324], tab sis txoj kev sib txawv tuaj yeem ua rau muaj kev sib txawv ntawm fibrils (Daim duab 6).
Piv txwv li, TDP-43, ib qho protein uas koom nrog ALS/FTD, raug mob fibrillation nrog lossis tsis muaj LLPS. Tseem, fibrillation kinetics nyob rau hauv ob qho tib si sib txawv, qhia txog kev koom tes ntawm cov txheej txheem nyuaj hauv fibrillation nyob rau hauv lub xub ntiag ntawm LPS [329].
Yog li ntawd, nws yuav yog ib qho tseem ceeb heev uas yuav tau nug ob peb nqe lus nug xws li seb cov fibrils tsim nrog lossis tsis muaj kev sib cais theem yog cov txheej txheem thiab ua haujlwm sib txawv ntawm ib leeg, lossis, tsuas yog muab tso rau, qhia fibril polymorphism. Txawm hais tias txawv LLPS cov xwm txheej lossis kev hloov pauv muaj lub luag haujlwm hauv kev txiav txim siab tus cwj pwm ntawm -Syn fibrils tsim?
Piv txwv li, cov kev hloov pauv pathogenic hauv FUS tau pom tias muaj cov khoom sib txawv ntawm lub cev piv rau cov tsiaj qus hom protein [327]. Cov kev tshawb pom no qhia tau hais tias, zoo ib yam li cov xwm txheej uas tsis yog-theem-sib cais qhov sib txawv ntawm cov kev daws teeb meem muab rau polymorphs [29], fibrils tsim nyob rau hauv cov txheej txheem sib cais sib txawv kuj tuaj yeem sib txawv (Daim duab 7).
Piv txwv li, -Syn theem sib cais raws li cov xwm txheej sib txawv, xws li muaj PTMs, kev hloov hauv tsev neeg, cov khoom me me, lossis cov hlau ions, tuaj yeem pom cov polymorphism thiab tsim ntau hom fibrils (Daim duab 7).
Txawm li cas los xij, qhov tshwm sim no tseem tsis tau txiav txim siab vim nws yuav xav tau kev nthuav dav ntawm fibrilsformed hauv cov tee dej.Peb ntseeg hais tias kev sib koom ua ke ntawm cov kab mob sib txawv nruab nrab thiab ntau txoj hauv kev sib sau ua ke pom nrog lossis tsis muaj LLPS tuaj yeem tsim lub hauv paus ntawm lub hauv paus ntawm polymorphism. .
Txawm li cas los xij, kev tshawb fawb ntxiv hauv daim teb no yuav tsum tau piav qhia txog kev koom tes ntawm heterogeneous nucleation thiab ntau txoj hauv kev sib sau ua ke rau fibrilpolymorphism. Kev txhim kho thiab kev siv ntau yam txuj ci biophysical tuaj yeem pab peb tau txais cov ntaub ntawv pom zoo txog cov xwm txheej molecular tshwm sim thaum lub sij hawm LLPS thiab tom qab kev loj hlob zuj zus.
8. Kev kho mob thiab kev kho mob cuam tshuam ntawm Polymorphism
Cov kev tshawb fawb tau sib tham hauv kev tshuaj xyuas muab cov pov thawj pom tseeb tias -Syn tuaj yeem tsim ntau hom polymorphs nrog cov qauv thiab cov khoom siv lom neeg sib txawv. Zoo ib yam li prions, qhov twg txhua tus kab mob prion yog encoded los ntawm kev sib txawv ntawm cov misfolded protein, txhua tus synucleinopathy kuj tseem cuam tshuam nrog cov qauv -Syn tshwj xeeb.
Txawm li cas los xij, ntau hom kab mob fibril rau tib cov protein ua rau muaj kev sib tw ntau hauv kev txhim kho tshuaj tiv thaiv kab mob neurodegenerative. Cov kev kho mob zoo li immunotherapy yuav yog qhov tshwj xeeb rau ib hom kab mob tshwj xeeb tab sis yuav tsis paub txog qhov sib txawv. Ib yam li ntawd, tsim cov tshuaj kho me me los yog tshuaj rau kev thaiv lossis ua kom qeeb ntawm cov txheej txheem protein sib sau ua ke yuav tsum tau kuaj xyuas rau ntau qhov sib txawv. Xav txog qhov nyuaj ntawm fibrils thiab lawv cov polymorphism, tsom rau monomeric -Syn tuaj yeem yog qhov kev xaiv.
Txawm li cas los xij, qhov ntawd tseem nyuaj vim qhov tsis txaus ntseeg ntawm cov protein.Txawm hais tias cov kev cov nyom no, kev kuaj pom thiab ua rau cov neeg mob tau txais txiaj ntsig -Syn strains yuav qhib lub qhov rais ntawm lub sijhawm rau kev nkag siab tob dua thiab ua tus cwj pwm ntawmsynucleinopathies. Nws yuav pab txhawb txoj kev loj hlob ntawm cov kev kho tshiab thiab ntau robustclassification systems ntawm synucleinopathies.
Hauv cov ntsiab lus no, cov txheej txheem rhiab heev zoo li PMCA [330], real-time quaking-induced conversion assay (RT-QuIC) [331] thiab HANdaiamyloid burst inducer (HANABI) [332] tau pab txhawb kom muaj zog -Synaggregates los ntawm CSF ntawm cov neeg mob ' hlwb. PMCA thiab RT-QuIC tau siv los sib cais ntawm PD / MSA thiab PD / DLB tus neeg mob tau los ntawm -Syn hom, raws li [52,333].
Kev siv cov tswv yim no yuav pab saib xyuas tus kab mob mus ntev thiab pab tau thaum ntxov thiab tshwj xeeb kev kuaj mob ntawm synucleinopathies. Tsis tas li ntawd, kev kho mob thiab kab mob sib txawv thiab cov neeg mob-rau-tus neeg mob heterogeneity pom hauv PD thiab cov kab mob cuam tshuam yuav cuam tshuam li cas cov neeg mob synucleinopathy yuav tsum tau kho. Txog tam sim no, txhua tus neeg mob PD tau txais tib hom kev kho mob, thiab kev sib cais ntawm cov neeg mob nyob ntawm seb lawv tau kis tus kab mob li cas thiab lawv cov tsos mob dab tsi tshwm sim.
Yog li ntawd, peb cia siab tias cov tshuaj thiab cov tshuaj kho tau tsim los rau cov hom kab mob -Syn tuaj yeem koom nrog kev siv cov tshuaj ib leeg lossis ib qho dej cawv ntawm cov tshuaj tiv thaiv ntau hom polymorphs lossis strains uas muaj nyob hauv tib neeg lub hlwb. Tsis tas li ntawd, ntau qhov tseem ceeb yuav tsum tau txiav txim siab raws li qhov xwm txheej ntawm tus kab mob, xws li kab mob, kab mob thiab kev kho mob, hom thiab qhov xwm txheej ntawm cov kab mob protein cuam tshuam, thiab cov kab mob kis tau zoo thaum kho cov neeg mob synucleinopathies.
Yog li ntawd, kev txheeb xyuas cov peev txheej kho mob thiab tsim cov tshuaj raws li kev sib raug zoo yog cov kauj ruam loj tom ntej mus rau kev tsim tshuaj tiv thaiv PD thiab cov kab mob cuam tshuam. Tsim kom muaj kev sib txuas ntawm kev nthuav tawm ntawm astrain thiab tus kab mob phenotype yuav muab kev nkag siab zoo rau kev tsim cov tswv yim zoo rau kev tawm tsam cov kab mob neurodegenerative.
Lwm qhov kev sib tw yog xa cov tshuaj rau lub hlwb los kho cov kab mob neurodegenerative, feem ntau ntsib kev poob qis vim kev txwv tsis pub ntshav-hlwb teeb meem [32]. Ntau qhov kev sim tau ua kom xa cov tshuaj los ntawm nanocarriers, txoj kev xa tshuaj ncaj qha, cuam tshuam ntawm cov ntshav-hlwb, thiab kev kho cov qia cell [33–37]. Txawm li cas los xij, tsis muaj ib qho kev kho mob twg muaj peev xwm kov yeej cov teeb meem tam sim no tag nrho [32].
9. Cov lus xaus thiab cov lus nug qhib
Tus cwj pwm zoo li prion-Syn tseem yog qhov tshwm sim enigmatic. Nws yog qhov xav tsis thoob li cas ib qho protein uas tsis muaj cov qauv tsim nyog tuaj yeem quav hauv ntau txoj kev sib txawv thiab txais kev sib haum xeeb uas ua rau muaj ntau yam pathologies.
Ntau cov lus nug tsis teb xav tau kev tshawb nrhiav ntxiv, txawm tias tom qab ua haujlwm zoo ntawm -Syn polymorphsand hom. Piv txwv li, dab tsi tsav qhov tsim ntawm -Syn strain nyob rau hauv muab cellular thiab ib puag ncig tej yam kev mob? Yuav ua li cas cov kab mob no tsom rau ntau hom cell thiab lub hlwb? Puas -Syn hom hloov zuj zus, hloov, lossis hloov kho nrog lub sijhawm nyob ntawm tus tswv tsev?
Lub xub ntiag ntawm lwm cov proteins, ligands, daim nyias nyias, los yog co-factors cuam tshuam rau kev tsim cov kab mob li cas? Puas yog-Syn hom muaj peev xwm hla-pom nrog ib leeg thiab ua rau cov kab mob sib xyaw ua ke? Puas -Syn hom cuam tshuam thiab thaiv kev nthuav tawm ntawm ib leeg, zoo ib yam li prions?
Puas yog nws ua tau, lossis peb puas muaj cov txheej txheem rhiab txaus rau kev ntxub ntxaug ntawm PD thiab MSA hom kab mob thaum ntxov ntawm kev kuaj mob? Xav txog qhov nthuav dav ntawm prion strain tshwm sim rau ntau lwm yam amyloidogenic proteins, nws tseem yuav tsim nyog kom nkag siab txog cov xwm txheej tseem ceeb hauv cov kab mob biology thiab cov tswv yim tsim nyog.
Sau Kev Pabcuam: Kev xav, SM, thiab SKM kev tshawb nrhiav (cov ntaub ntawv tshuaj xyuas); SM; LG; RB thiab ASS; kev sau ntawv-kev npaj ua ntej, SM; LG; RB thiab ASS; sau-reviewand editing, SM; LG; RB; ASS thiab SKM; kev pom, SM; kev tswj xyuas qhov project, SM, thiab SKM; kev saib xyuas, SM, thiab SKM; Kev nrhiav nyiaj txiag, SKM, SM, thiab SKM yog cov neeg sau ntawv sib luag. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Kev Kawm Txuj Ci: Qhov kev tshawb fawb no tau txais nyiaj los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv Biotechnology (DBT) [BT/PR22749/BRB/10/1576/2016], Tsoomfwv Is Nrias teb.
Institutional Review Board Statement: Tsis siv tau.
Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.
Cov Lus Qhia Muaj Cov Ntaub Ntawv: Tsis siv tau.
Kev lees paub: Cov kws sau ntawv lees paub lub Department of Biotechnology (DBT), Tsoomfwv Is Nrias teb rau kev txhawb nqa nyiaj txiag. Peb ua tsaug rau Pradeep Kadu rau nws txoj kev pab tsim cov duab. SM ua tsaug rau University Grants Commission ntawm Is Nrias teb rau nws txoj kev sib raug zoo.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
Cov ntawv luv
-synuclein (-Syn), Parkinson's disease (PD), ntau qhov system atrophy (MSA), dementia nrog Lewy lub cev (DLB), Parkinson's Disease Dementia (PDD), Lewy lub cev (LBs), Lewy neurites (LNs), Alzheimer's disease (AD ), Glial cytoplasmic inclusions (GCIs), post-translational modifications (PTMs), wild-type (WT), cryo-electron microscopy (cryo-EM), solid-state NMR (ssNMR) spectroscopy; transmission electron microscopy (TEM), atomic force microscopy (AFM), ncig dichroism (CD), dorsal motor nucleus ntawm vagus paj (DMV), enteric paj hlwb (ENS); -Synuclein (xws li); -synuclein (-Syn); Protein misfolding cyclic amplification (PMCA); Liquid-Liquid Phase Separation (LLPS).
Cov ntaub ntawv
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