Kev laus tuaj yeem ua rau poob ntawm cell adaptability thiab poob ntawm kev pom cov protein ua haujlwm. Ntau lub hnub nyoog txo qis cov kab mob, suav nrog Alzheimer39; tus kab mob thiab Parkinson39; tus kab mob, yog tshwm sim los ntawm cov protein sib sau ua ke, uas yog qhov tshwm sim ntawm cov protein folding yuam kev. Txawm li cas los xij, cov txheej txheem ntawm kev laus ua rau cov protein sib sau ua ke tseem yog lub thawv dub mus rau qhov loj. Nyob rau hauv ib txoj kev tshawb fawb tshiab tsis ntev los no tau luam tawm nyob rau hauv phau ntawv journal Nature, cov kws tshawb fawb ntawm Stanford University muab qhov teeb meem rau qhov tseeb tias cov txheej txheem tsim cov proteins tshiab tsis zoo los ntawm lub hnub nyoog.
Txoj kev tshawb no tau luam tawm nyob rau hauv phau ntawv journal Nature (kawg cuam tshuam: 49.962) thaum Lub Ib Hlis 19, 2022
Txhawm rau daws qhov teeb meem no, cov kws tshawb fawb ntawm Judith Frydman39; lub chaw kuaj mob, tus thawj coj ntawm Donald Kennedy ntawm Academy of Humanities ntawm Stanford University, tau tsom mus rau qhov muaj hnub nyoog cuam tshuam li cas ntawm ribosomes. Ribosomes yog cov tshuab cellular lub luag haujlwm rau kev hloov cov tub txib RNA rau hauv cov protein. Lawv siv ob tus qauv paub txog tib neeg kev laus, poov xab thiab nematodes. Los ntawm kev sib txuas cov ntaub ntawv sim thiab suav nrog, lawv pom tias kev ua haujlwm ntawm ribosomes degraded nrog lub hnub nyoog. Nrog rau kev loj hlob ntawm lub hnub nyoog, lub load ntawm cov proteins uas tsis zoo yuav nce, uas ua rau cov kev tswj tsis ua hauj lwm tiv thaiv mechanism uas yuav tiv thaiv cov protein aggregation tsis zoo.
quot; Peb twb paub lawm hais tias protein aggregation nrog lub hnub nyoog yog ib qho teeb meem txuam nrog ntau yam kab mob.quot; quot; Ib qho kev txo qis hauv kev kawm tob txog cov kab mob biology ntawm cov kab mob no thiab cov txheej txheem uas ua rau lawv tuaj yeem pab peb txiav txim siab zoo dua txog cov kev kho mob twg yuav zoo ua ntej kuaj lawv, quot; hais tias Kevin Stein, thawj tus sau ntawm daim ntawv thiab ib tug qub postdoctoral scholar ntawm lub Frydman kuaj
Lub sijhawm tsis muaj zog
Thaum folded kom raug, cov proteins ua lawv txoj haujlwm thiab nyob twj ywm hauv cov cellular ib puag ncig. Nyob rau hauv sib piv, misfolded proteins tsis ua hauj lwm kom zoo thiab nyiam mus rau ib leeg thiab lwm yam proteins, thaiv cov txheej txheem cellular thiab tsim cov tshuaj lom aggregates. Protein aggregation yog qhia meej meej nrog ntau yam kab mob ntawm cov laus, suav nrog Alzheimer39; tus kab mob, Parkinson39; tus kab mob, frontotemporal dementia, Huntington39; tus kab mob thiab als (amyotrophic lateral sclerosis)
Txhawm rau tiv thaiv kom tsis tu ncua ntawm misfolded proteins, hlwb muaj qhov tshwj xeeb quot; zoo tswjquot; mechanism kho los yog degrade misfolded proteins. Cov kev tshawb fawb yav dhau los tau qhia tias qhov tsis xws ntawm cov txheej txheem no tuaj yeem ua rau polymerization. Txoj kev tshawb no yog thawj zaug uas qhia tau hais tias folding tsis xws luag hauv kev laus pib thaum ntxov ntawm cov protein, thaum nws tau tsim los ntawm ribosomes. Txij li thaum ribosomes tas li tsim cov protein ntau ntau, cov teeb meem no tuaj yeem ua rau cov pob zeb tom ntej xws li kev ua haujlwm tsis zoo.
quot; Ib lub sij hawm tseem ceeb tshaj plaws thiab tseem ceeb tshaj plaws ntawm lub neej ntawm cov protein txo nws yog feem ntau ua rau misfolding txo yog thaum nws ua, quot; hais tias Frydman, tus xibfwb ntawm biology thiab noob caj noob ces
Ua ntej, cov kws tshawb fawb tau siv cov txheej txheem hu ua ribosome profileing, uas tso cai rau lawv kom pom tseeb tias ribosomes txav mus rau tus tub txib RNA thaum txhais lus. Cov kws tshawb fawb tau sau cov ntaub ntawv ntawm tag nrho cov noob txhais hauv cov tub ntxhais hluas thiab laus Caenorhabditis elegans thiab cov poov xab. Lawv pom tias nyob rau hauv cov laus hlwb, ribosomes ib ntus txav qeeb dua thiab muaj feem ntau yuav stagnate thiab sib tsoo. Raws li qhov xav tau, cov kws tshawb nrhiav pom tias qhov poob ntawm qhov kev ua tau zoo ribosome tau zoo ib yam nrog kev nce hauv kev laus raws li kev sib sau ua ke ntawm misfolded proteins. Ib qho kev pom tseem ceeb yog tias qhov nce ntawm stagnation thiab misfolding overwhelms qhov zoo tswj tsis ua hauj lwm pov hwm ntawm cell tu thiab tshem tawm.
quot; Muaj ob qhov xwm txheej uas kev laus ua rau muaj qhov tsis txaus ntseeg thiab nce ribosome kev sib tsoo, tab sis lub xov tooj ntawm tes poob nws txoj kev nyab xeeb, quot; Stein piav qhia.
Hauv kev ua raws li txo cov kev sim ntawm cov kab mob hauv online, cov kws tshawb fawb pom tias txawm tias tag nrho cov khoom tsim tawm tshiab nrog cov kev hloov pauv hloov thaum muaj hnub nyoog qis heev (10 feem pua), cov nyhuv me me no tseem txaus rau overburden cov kev tswj xyuas zoo thiab ua rau muaj kev loj hlob. polymerization, uas tuaj yeem rhuav tshem ntau cov khoom sib txawv ntawm tes lossis cov txheej txheem.
quot;Txhua lub xovtooj ntawm tes feem ntau tsim ntau lab ntawm cov proteins uas tau txhais tshiab, quot; Frydman hais tias. quot; Yog li ntawd, nrog rau hnub nyoog, me me hloov nyob rau hauv folding efficiency yuav escalate nyob rau hauv ib tug vicious vajvoog, nyob rau hauv uas txhais lus tsis xws luag ua rau lub cev overload, uas ua rau kom cov protein aggregates nrog lub hnub nyoog, uas yog lawv tus kheej toxic.quot;
Txhawm rau ua qhov tsis zoo, dhau los ntawm kev sim ntxiv nrog cov poov xab thiab Caenorhabditis elegans, cov kws tshawb fawb pom tias cov teeb meem no cuam tshuam rau cov proteins uas siv los ntawm cov hlwb los pab txhais thiab kho cov teeb meem tsis zoo.
Ntau lab cov lus nug
Txawm hais tias txoj kev tshawb no nthuav tawm qee qhov kev nkag siab zoo rau cov txheej txheem ntawm kev laus thawj zaug, nws txhawb ntau cov lus nug yav tom ntej. Tej zaum qhov tseem ceeb tshaj plaws: vim li cas kev laus cuam tshuam rau ribosomes? Tsis tas li ntawd, yuav ua li cas?
Muab qhov zoo sib xws ntawm kev laus hauv cov poov xab, Caenorhabditis elegans thiab lwm yam kab mob, cov kws tshawb fawb tau pom zoo tias lawv qhov kev tshawb pom tseem yuav raug muab txhais ua tib neeg siv. Ib qho kev taw qhia ntawm kev ua haujlwm yav tom ntej yog siv cov kev nkag siab ntawm txoj kev tshawb no rau kev txhim kho cov kev kho mob uas muaj hnub nyoog txo cov kab mob cuam tshuam nrog kev sib sau ua ke ntawm cov protein. Interestingly, qhov kev tshawb fawb no qhia tau hais tias kev hloov pauv ntawm lub neej txuas ntxiv tuaj yeem quot;restorequot; ribosomal muaj nuj nqi ntawm aging poov xab.
quot;This is just the beginning of a very fascinating future,quot; said FabI á n Morales Polanco, co reduce author of the study and a postdoctoral scholar at the Frydman laboratory. quot;We set a precedent for new things, and then there will be millions of problems reduce and possibly hundreds of papers.quot;
