Alpha-Klotho nyob rau hauv Parkinson's Disease: Ib Qhov Kev Pom Zoo Ntawm Kev Tshawb Fawb Txog Kev Tshawb Fawb Thiab Kev Muaj Peev Xwm Kev Kho Mob
Jul 14, 2023
-Klotho protein (KL) tau tshawb pom ntau dua 20 xyoo dhau los thiab tam sim ntawd tau tshwm sim los ua tus tswj hwm ntawm cov txheej txheem kev laus, uas ua haujlwm raws li kev tiv thaiv kev laus. Nws tau nthuav tawm los ntawm tag nrho tib neeg lub cev, sawv cev rau choroid plexus thiab lub raum raws li qhov chaw nquag tshaj plaws ntawm lub hauv paus paj hlwb (CNS) thiab qib periphery raws li. Rau qhov tsawg dua, kuj yog cov qog parathyroid, cov ntaub so ntswg adipose, thiab lub siab qhia KL.
Glycoside ntawm cistanche tuaj yeem ua rau muaj kev ua haujlwm ntawm SOD hauv plawv thiab daim siab cov ntaub so ntswg, thiab txo cov ntsiab lus ntawm lipofuscin thiab MDA hauv txhua cov ntaub so ntswg, tshem tawm ntau yam reactive oxygen radicals (OH-, H₂O₂, thiab lwm yam) thiab tiv thaiv DNA puas. los ntawm OH-radicals. Cistanche phenylethanoid glycosides muaj peev xwm tshem tawm cov dawb radicals, muaj peev xwm txo tau ntau dua li cov vitamin C, txhim kho cov haujlwm ntawm SOD hauv cov phev ncua, txo cov ntsiab lus ntawm MDA, thiab muaj qee yam kev tiv thaiv ntawm cov phev ua haujlwm. Cistanche polysaccharides tuaj yeem txhim kho kev ua haujlwm ntawm SOD thiab GSH-Px hauv erythrocytes thiab ntsws cov ntaub so ntswg ntawm cov nas senescent sim los ntawm D-galactose, nrog rau txo cov ntsiab lus ntawm MDA thiab collagen hauv lub ntsws thiab ntshav, thiab nce cov ntsiab lus ntawm elastin, muaj Cov nyhuv scavenging zoo ntawm DPPH, ncua lub sijhawm ntawm hypoxia hauv cov nas senescent, txhim kho cov haujlwm ntawm SOD hauv cov ntshav, thiab ncua lub physiological degeneration ntawm lub ntsws hauv kev sim cov nas nrog cellular morphological degeneration, kev sim tau pom tias Cistanche muaj peev xwm antioxidant zoo. thiab muaj peev xwm los ua ib qho tshuaj tiv thaiv thiab kho cov kab mob ntawm daim tawv nqaij laus. Nyob rau tib lub sijhawm, echinacoside hauv Cistanche muaj lub peev xwm tseem ceeb txhawm rau txhawm rau DPPH dawb radicals thiab muaj peev xwm tshem tawm cov pa oxygen reactive thiab tiv thaiv dawb radical-induced collagen degradation, thiab kuj muaj kev kho zoo ntawm thymine dawb radical anion puas.
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KL yog ib qho transmembrane protein ua ib qho tseem ceeb co-receptor rau fibroblast kev loj hlob receptors, tab sis, feem ntau, nws kho ob peb txoj hauv kev molecular thiab kev ua haujlwm lom neeg ntawm ntau theem. Txawm tias muaj ib daim ntawv soluble, originated los ntawm extracellular domain cleavage, uas circulates nyob rau hauv tib neeg cov kua, tso cai rau ib tug systemic signaling. Txawm hais tias tag nrho cov ntaub so ntswg tshwj xeeb tsis tau qhia meej meej, muaj cov pov thawj ruaj khov uas KL tswj hwm cov ntxhia hauv homeostasis thiab cov txheej txheem hauv cov metabolism hauv. Hauv CNS, hloov pauv, nws suav nrog cov qauv dav dav thiab cov teebmeem neuroprotective (Cheikhi li al., 2019).
Kev sim txo qis-kev tswj hwm ntawm KL hauv cov qauv ua rau muaj kev laus ntxov ntxov, nrog rau cov yam ntxwv neurodegenerative, kev koom tes hauv visceral thiab musculoskeletal, thiab luv luv lifespan. Hloov pauv, qhov overexpression ua rau txhim kho kev paub thiab neuroprotective los tiv thaiv kev laus; ib yam nkaus, kev tswj hwm cov protein tiv thaiv thiab txwv tsis pub muaj kev puas tsuaj nyob rau hauv cov qauv sib txawv ntawm cov kab mob mob / mob ntev (lub raum thiab lub plawv raug mob) los ntawm cov tshuaj tiv thaiv antioxidant thiab tiv thaiv kab mob (Cheikhi li al., 2019).
Ntau qhov kev tshawb fawb tau txuas cov qib siab dua KL kom tau txais kev noj qab haus huv zoo dua, txo qis kev pheej hmoo rau cov kab mob tsis zoo, thiab kev cia siab ntev rau tib neeg. Contrariwise, qhov txo qis tau cuam tshuam nrog cov kab mob plawv thiab cov xwm txheej macrovascular hauv cov neeg mob ntshav qab zib hom 2, lossis mob raum tsis ua haujlwm. Ntxiv mus, nyob rau hauv ntau yam sab hauv, muaj feem xyuam rau lub hnub nyoog, peripheral KL theem tau correlated nrog rau qhov hnyav ntawm chav kho mob thiab prognosis. Raws li, KL tau nce qhov hnyav raws li kev tshawb fawb biomarker ntawm cov hnub nyoog ntsig txog cov ntaub so ntswg ua haujlwm tsis zoo, tab sis kuj nyob rau hauv cov ntsiab lus ntawm cov kev kho mob muaj peev xwm tiv thaiv kev poob qis (Cheikhi li al., 2019).
Cov kab mob neurodegenerative, uas yog Alzheimer's disease (AD) thiab Parkinson's disease (PD) yog ob hom kab mob ntau tshaj plaws, ua rau muaj feem cuam tshuam txog hnub nyoog. Raws li kev cia siab, KL txoj kev koom nrog txawm tias nyob rau hauv cov xwm txheej no. Muaj pov thawj tias KL txo qis hauv lub hlwb ntawm cov neeg mob AD thiab cov qauv nas; Ib yam nkaus, qhov sib txawv ntawm KL kev ua haujlwm thiab kev kho mob phenotype lossis amyloid- thiab tau lub nra tau raug tshawb pom (Belloy li al., 2020). Hais txog PD, hloov pauv, thawj cov ntaub ntawv tsuas yog tuaj txog, tab sis lawv tau txais kev tshoov siab tam sim ntawd los ntawm qhov muaj feem cuam tshuam rau kev kho mob.
Hauv qhov kev xav no, yog li ntawd, peb yuav xaus cov pov thawj tam sim no ntawm lub luag haujlwm ntawm KL hauv PD, xa mus rau cov kev tshawb fawb tseem ceeb thiab kev kho mob; tom qab ntawd, peb yuav cia siab tias yuav muaj kev nce qib ntxiv tom ntej los ua KL txawm tias muaj txiaj ntsig biomarker lossis tus neeg sib tw kho lub hom phiaj rau PD.
Kev koom tes ntawm KL txoj hauv kev hauv PD thiab muaj feem cuam tshuam rau kev kho mob:PD yog cov kab mob neurodegenerative uas nws cov kab mob pathological yog qhov poob ntawm dopaminergic hlwb los ntawm substantia nigra pars compacta thiab intraneuronal tsub zuj zuj ntawm -synuclein zoo Lewy lub cev. Cov neeg mob nrog PD raug kev txom nyem los ntawm kev loj hlob, kev xiam oob qhab, thiab heterogeneous syndrome, nrog rau cov cim qhia lub cev muaj zog (bradykinesia, rigidity, tremor, postural thiab gait disturbances) thiab ntau yam ntawm cov tsos mob uas tsis yog lub cev muaj zog. Muaj cov kev kho mob rau PD yog raws li kev hloov dopamine, tsuas yog muab cov tsos mob zoo xwb. Cov kev kho mob-hloov kho tau zoo, qhov tseeb, tseem tsis muaj, nrog rau cov kab mob txhim khu kev qha biomarkers txhawb kev kuaj mob, kev ntsuas kev ntsuas, thiab kev soj ntsuam kev loj hlob. Kev tshawb pom ntawm biomarkers thiab kev txhim kho cov kev kho tshiab ob leeg nyob ntawm kev nkag siab tob dua ntawm cov txheej txheem pathogenic ntawm PD. Tshwj xeeb, nws yuav tsum tau txheeb xyuas cov molecules, uas nws qhov kev ntsuam xyuas ntau hauv cov ntaub so ntswg thiab cov kua dej tuaj yeem qhia txog cov xwm txheej hauv qab no, tab sis qhov ntawd kuj tseem tuaj yeem ua lub hom phiaj rau kev cuam tshuam rau kev cuam tshuam rau neurodegeneration thiab kab mob kev loj hlob (Sancesario li al., 2021). Hauv kaum xyoo dhau los, kev tshawb fawb los ntawm preclinical modelandhum ib np ntawm I e nt sonthe kev koom tes ntawm KL hauv PD txhawb kev tshawb fawb hauv daim teb no, qhia txog qhov muaj peev xwm kho mob rau KL txoj hauv kev hauv PD.
Cov kev sim ntawm cov qauv tsiaj tau pom tias muaj cov khoom tiv thaiv neuroprotective ntawm KL hauv PD, feem ntau ua haujlwm los ntawm kev txo qis ntawm Piergiorgio Grillo, Michele Basilicata, Tommaso Schirinzi * cov kev hloov pauv neuropathological, halting ntawm cov kab mob tseem ceeb (oxidative stress thiab neuroinflammation), thiab kev hloov kho ntawm synaptic plasticity. (Chihi et al., 2019). Tshwj xeeb, Kosakai et al. (2011) pom tias KL-tsis muaj nas, piv rau cov tsiaj qus littermates, muaj qhov txo qis ntawm mesencephalic dopaminergic neurons los ntawm ob qho tib si substantia nigra pars compact thiab ventral tegmental cheeb tsam, nrog rau qib qis ntawm striatal dopamine. Ntawm qhov tod tes, kev txhaj tshuaj intraperitoneal ntawm KL hauv PD nas qauv qhia transgenic -synuclein ua rau txhim kho kev txawj ntse thiab kev coj tus cwj pwm, thiab txhim kho synaptic plasticity hauv hippocampus (Leon li al., 2017). Ib yam nkaus li, kev txhaj tshuaj intracerebroventricular KL hauv 6-hydroxydopamine lesioned nas qauv ameliorated lub cev muaj zog tsis txaus thiab tempered down neuropathology, tso cai rau lub nra qis ntawm -synuclein, malondialdehyde, reactive oxygen hom, thiab glial fibrillary acid protein txuam nrog. Cov tsos mob me me ntawm cov neurodegenerative (Baluchnejadmojarad li al., 2017).
Tsis ntev los no, cov ntaub ntawv kho mob kuj tau txais thiab cov duab ntawm KL qhia tau piav qhia hauv biofluids ntawm PD cov neeg mob. Sancesario et al. (2021) muab kev ntsuas ua ke ntawm KL hauv cerebrospinal kua (CSF) thiab cov ntshav ntawm PD pawg, nrhiav cov qib sib txawv hauv ob qhov chaw. Namely, KL qib siab dua li poj niam txiv neej / hnub nyoog sib haum xeeb tswj kev noj qab haus huv hauv CSF, thiab qis dua hauv cov ntshav. Tsis muaj kev sib raug zoo tshwm sim ntawm ob lub pas dej los yog nrog cov ntshav-hlwb thaiv kev ua haujlwm tsis zoo, nthuav tawm KL qhia txawv ntawm theem nruab nrab thiab sab hauv, uas cuam tshuam txog cov txheej txheem pathophysiological sib txawv. Qhov tseeb, hauv CSF, qib ntawm KL thiab cov ntawm tag nrho -synuclein tau sib cuam tshuam, qhia tias kev nthuav qhia ntau ntxiv ntawm KL hauv CNS tuaj yeem yog cov lus teb tiv thaiv rau kev tso tawm ntawm Lewy lub cev. Kev txo qis hauv cov ntshav, hloov pauv, tau suav tias yog qhov tshwm sim ntawm kev mob o thiab oxidative kev nyuaj siab, ob lub PDrelated phenomena uas tuaj yeem cuam tshuam cov kab mob peripheral ntawm KL, raws li tau piav qhia hauv lwm cov kab mob ntev-degenerative. Kev tshawb pom los ntawm Sancesario et al. (2021) los ntawm PD pawg ntawm cov kab mob thaum ntxov (hnub nyoog 59 ± 11 xyoo, kab mob ntev 3.5 ± 3.9 xyoo), thaum, nyob rau hauv txoj kev xav, cov lus teb tiv thaiv yuav ua tau zoo dua, vim tias CSF nce ntawm KL hauv kev koom tes nrog kev sib txuam synucleinopathy. qhia.
Hauv qhov loj dua thiab ntau qhov chaw kho mob-ua ntej PD cohort, hloov, Zimmermann li al. (2021) pom tias CSF KL qib tau txo qis piv rau kev tswj hwm kev noj qab haus huv thiab txo qis nyob rau tib lub sijhawm nrog kev cuam tshuam ntawm lub cev muaj zog. Ib yam nkaus li, hauv ib pab pawg neeg mob laus dua cov neeg hauv Sancesario pawg neeg, KL plasma qib, ntsuas los ntawm kev ntsuas immunoprecipitation-immunoblotting, zoo ib yam li kev tswj hwm kev noj qab haus huv (Kakar li al., 2021). Txawm hais tias muaj kev txwv vim muaj ntau yam kev ntsuam xyuas thiab cov qauv kev kawm sib txawv, qhov muaj peev xwm ntawm KL raws li biomarker rau PD tau tshwm sim.
Qhov tseeb, hauv CNS, KL kev qhia zoo li hloov pauv nyob ntawm theem kab mob lossis kev kho mob tag nrho. Nyob rau theem pib, peb yuav pom qhov nyiaj them rov qab, uas tej zaum yuav pab tiv thaiv kev loj hlob ntawm neurodegeneration (Sancesario li al., 2021). Raws li qhov tshwm sim, PD cov neeg mob uas muaj KL-VS haplotype, uas muaj cov protein ua haujlwm tsawg dua KL, tsim cov phenotype aggressive, nrog rau lub cev muaj zog loj dua thiab kev paub tsis meej ntxov (Zimmermann li al., 2021). Nrog rau kev nce qib ntawm PD, cov txheej txheem them nyiaj poob qis, thiab ob qho tib si neurodegeneration thiab neuroinflammation kis (Sancesario li al., 2021), nrog rau kev cuam tshuam tom qab ntawm CNS KL qhia thiab kev poob qis ntawm kev kho mob. CSF KL qib tuaj yeem qhia txog qhov muaj peev xwm ntawm cov kab mob neuroprotective ntawm lub paj hlwb, uas yog qhov tseem ceeb rau stratify cov neeg mob, tshwj xeeb tshaj yog thaum pib ntawm tus kab mob, thiab, thaum kawg, kho cov kev kho mob. Nyob rau hauv lub periphery, es tsis txhob, KL feem ntau yog tsim los ntawm lub raum thiab ib tug txo ntawm circulating theem tau ntsuas nyob rau hauv cov neeg mob uas muaj lub raum mob, ntshav qab zib mellitus, thiab cov kab mob ntev-degenerative, feem ntau muaj kev kwv yees tus nqi siab hauv kev kho mob (Sancesario li al., 2021). Ib yam li ntawd, hauv PD, cov ntshav KL tuaj yeem ua haujlwm raws li kev nyeem cov txheej txheem tseem ceeb ntawm cov txheej txheem pathogenic, xws li oxidative kev nyuaj siab thiab o, uas tuaj yeem pab tau zoo rau tus cwj pwm zoo ntawm tus kheej ntawm txhua tus neeg mob (Daim duab 1).
Tsis ntev los no nws tau tsa qhov kev xav tias, qee zaum, PD pathology tuaj yeem pib los ntawm enteric lossis peripheral autonomic paj hlwb, thiab nce mus rau CNS feem ntau ntawm cov hlab ntsha vagus ("lub cev thawj qhov kev xav") (Horsager li al. , 2020). Lub plab o muaj lub luag haujlwm tseem ceeb hauv PD pathogenesis lossis kev loj hlob, thiab tseem tuaj yeem ua ntej cov theem ntawm tus kabmob (Brudek, 2019). Ntawm kev txaus siab, cov theem ntawm KL txo qis hauv cov plab hnyuv thiab cov kab mob plab hnyuv (Thurston li al., 2010), yog li txhawb lub tswv yim hais tias circulating KL qhia txog cov xwm txheej tshwm sim los ntawm CNS tab sis txuas rau PD mechanisms. Cov hlwb enteric, tshwj xeeb tshaj yog nyob rau hauv txoj hnyuv, kuj qhia KL. Cov kab mob plab hnyuv txawv txav ntawm KL tau raug cuam tshuam nrog cov kab mob hauv zos; uas yog, txoj kev tshawb fawb tsis ntev los no tau pom tias cov qog nqaij hlav qog nqaij hlav hauv plab muaj qis dua KL piv rau cov ntaub so ntswg. Hloov pauv, KL overexpression lossis kev tswj xyuas sab nraud inhibits qog nqaij hlav cancer (Arbel Rubinstein li al., 2019).
Cov ntaub ntawv no tau tsim lub hauv paus rau kev ntsuam xyuas ncaj qha ntawm KL hauv plab hnyuv ntawm cov neeg mob PD rau kev kho mob. Dhau li ntawm kev kuaj pom ncaj qha ntawm KL hauv cov kab mob enteric, plab hnyuv KL yuav raug ntsuas zoo dua hauv cov chaw nkag tau yooj yim dua, xws li lub qhov ncauj. KL tau nthuav tawm los ntawm lub qhov ncauj mucosa thiab cov qog ua kua qaub (Tai li al., 2019), uas twb sawv cev rau qhov muaj txiaj ntsig ntawm cov kua dej biomarkers hauv PD (Bougea li al., 2019). Ib yam li ntawd, qhov kev hloov pauv ntawm KL qib hauv plab nce siab raws li qhov tshiab, kev xav, kev kho kab mob-hloov kho rau PD, tsom mus rau ib qho ntawm cov chaw ntxov tshaj plaws ntawm neuropathology.
Cov lus xaus: Hauv kev xaus, peb muaj cov pov thawj thawj zaug uas qhov kev qhia ntawm KL tuaj yeem cuam tshuam los ntawm qhov nruab nrab lossis cov txheej txheem ntawm cov txheej txheem molecular tseem ceeb hauv qab ntawm ntau theem ntawm PD. Kev ntsuas ntawm KL hauv cov ntaub so ntswg sib txawv (CSF, ntshav, lwm cov ntaub so ntswg peripheral) yog li qhia txog lub nra ntawm cov kab mob pathogenic rog thiab muaj qee qhov kev sim ua kom them nyiaj, uas yog qhov tseem ceeb los txheeb xyuas lub sijhawm zoo-qhov rais rau kev kho kom zoo I nte r ve nt kuv on s. M o re o ve r, qhov rov txhawb nqa cov ntaub ntawv qhia KL raws li tus neeg sib tw muaj txiaj ntsig lub hom phiaj rau kev kho tshiab hauv PD.
Piergiorgio Grillo, Michele Basilicata, Tommaso Schirinzi *
Unit of Neurology, Department of Systems Medicine, University of Roma Tor Vergata, Rome, Ltalis (Grillo P, Schirinzi T) Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy (Basilicata M)
* Cov lus teb rau:Tommaso Schirinzi, MD, Ph.D., t.schirinzi@yahoo.com los yog tommaso.schirinzi@uniroma2.it.
Hnub tim:Lub Kaum Hli 29, 2021
Hnub txiav txim:Kaum Ob Hlis 7, 2021
Hnub lees txais:Kaum Ob Hlis 21, 2021
Hnub tim ntawm lub vev xaib tshaj tawm:Lub Plaub Hlis 29, 2022
Qhib cov lus qhia nkag:Nov yog phau ntawv xov xwm qhib, thiab cov khoom raug muab faib raws li cov ntsiab lus ntawm Creative Commons AttributionNonCommercial-ShareAlike 4.0 Daim ntawv tso cai, uas tso cai rau lwm tus los remix, tweak, thiab tsim los ntawm kev ua haujlwm tsis yog lag luam, tsuav yog cov credit tsim nyog tau muab thiab cov kev tsim tshiab tau tso cai raws li cov ntsiab lus zoo ib yam.
Qhib cov neeg soj ntsuam xyuas:Katarzyna Kuter, Maj Institute of Pharmacology, Polish Academy of Sciences, Poland; Melinda Barkhuizen, Philip Morris International Management SA, Netherlands.
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