Los ntawm Cocer Peptides 
30 hnub dhau los
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
SS-31, tseem hu ua Elamipretide, yog ib qho tshiab aromatic cationic peptide. SS-31 tuaj yeem hla cov hlab ntsha-hlwb thaiv kev ywj pheej, ib qho cuab yeej uas ua rau nws tsim nyog rau kev kho mob ntawm lub paj hlwb. Cov ntshav-hlwb barrier yog ib qho tseem ceeb tiv thaiv barrier rau lub hauv paus paj hlwb, nrog rau feem ntau cov tshuaj tawm tsam kom hla nws. Txawm li cas los xij, SS-31 kov yeej qhov kev txwv no, ncaj qha mus txog qhov chaw ntawm neural puas thiab muab kev cia siab rau kev kho ntawm neural cell puas. Nws belongs rau cov chav kawm ntawm me me-molecule peptides, nrog ib tug kuj tsis tshua muaj molecular hnyav, uas confers nws nrog zoo mus thiab bioavailability nyob rau hauv lub cev. Cov cations nqa los ntawm SS-31 ua rau nws cuam tshuam nrog cov khoom tsis zoo ntawm cov khoom siv roj ntsha, tshwj xeeb tshaj yog cov tsis zoo them nyiaj sab hauv daim nyias nyias phospholipids ntawm mitochondria. Qhov kev sib khi tshwj xeeb no tso cai rau SS-31 tuaj yeem khaws cia hauv mitochondria, yog li siv nws cov kev tswj hwm kev ua haujlwm ntawm mitochondrial.
Daim duab 1 Mechanism of action of SS-31 tiv thaiv kab mob raum.
Mechanism ntawm Action
Kev cai ntawm Mitochondrial Function
Mitochondria, raws li lub cell lub zog lub zog, ua lub luag haujlwm tseem ceeb hauv cellular ciaj sia taus thiab metabolism. SS-31, nrog nws cov qauv cationic, tuaj yeem nthuav dav hauv cov khoom tsis zoo hauv daim nyias nyias phospholipids ntawm mitochondria, yog li txhim kho mitochondrial ua pa. mitochondrial respiratory saw yog ib txoj hauv kev tseem ceeb rau cellular zog tsim (ATP). SS-31 optimizes kev ua haujlwm ntawm cov proteins uas muaj feem xyuam rau hauv cov kab mob ua pa, txhim kho kev thauj mus los ntawm electron, yog li txhawb ATP synthesis thiab muab cov hlwb kom muaj zog txaus los tswj cov kev ua haujlwm ntawm lub cev xws li kev faib tawm ntawm tes, sib txawv, thiab kev thauj khoom.
SS-31 activates mitochondrial biogenesis nyob rau hauv neurons, txhawb cov tiam tshiab mitochondria. Thaum cov hlwb ntsib kev puas tsuaj lossis kev ntxhov siab, tiam tshiab ntawm mitochondria pab rov ua kom puas lossis tsis ua haujlwm mitochondria, tswj kev noj qab haus huv ntawm cov neeg mitochondria hauv lub cell. Nws kuj tseem txhim kho mitochondrial autophagy, cellular mechanism rau tshem tawm puas mitochondria. Yog tias cov mitochondria puas tsis tau tshem tawm sai, lawv tso tawm ntau cov pa oxygen reactive (ROS), ntxiv rau cov hlwb puas. SS-31 zoo txo ROS ntau lawm los ntawm kev txhim kho mitochondrial autophagy, yog li tiv thaiv cov hlwb los ntawm oxidative kev nyuaj siab puas.
Inhibiting inflammatory teb
Hauv ntau cov txheej txheem kev puas tsuaj ntawm tes, cov lus teb inflammatory feem ntau nrog rau kev puas tsuaj. Cytoplasmic phospholipase A2 (cPLA2), uas yog thawj tus neeg nruab nrab ntawm neuroinflammation, rhuav tshem cov membrane phospholipids ntawm sn-2 txoj hauj lwm ntawm lysosomes nyob rau hauv pathological tej yam kev mob, tsim lysophospholipids thiab ω3 polyunsaturated fatty acids, ua rau lysosomal perme (Lus soomal perme) tsim ib puag ncig. SS-31 tuaj yeem txo qis cov kev qhia theem ntawm phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), inhibit phosphorylation ntawm cPLA2, yog li txo qis kev tsim cov inflammatory mediators thiab alleviating kev puas tsuaj los ntawm inflammatory teb rau cov hlwb.
Hauv kev tshawb fawb ntawm sepsis-induced myocardial raug mob, SS-31 tau pom tias inhibit qhov ua kom NF-κB thiab NLRP3, yog li txhim kho myocardial inflammatory teb. NF-κB yog tus tswj xyuas qhov tseem ceeb ntawm cov kab mob inflammatory, thaum NLRP3 yog ib qho tseem ceeb ntawm cov kab mob inflammasome. Lawv qhov ua kom ua rau muaj kev tso tawm ntau ntawm cov kab mob inflammatory, xws li IL-6, IL-1β, thiab TNF-α. Los ntawm inhibiting qhov ua rau ntawm ob yam tseem ceeb no, SS-31 txo cov kev qhia theem ntawm inflammatory yam, alleviates inflammatory kev puas tsuaj rau myocardial hlwb, thiab tswj lawv ib txwm ua hauj lwm.
Txhawb nqa autophagy thiab inhibiting pyroptosis
Autophagy yog ib qho tseem ceeb ntawm kev tiv thaiv tus kheej hauv cov hlwb uas tshem cov organelles puas, misfolded proteins, thiab lwm yam teeb meem. Hauv kev tshawb fawb txog kev raug mob ntawm tus txha caj qaum, nws tau pom tias SS-31 txhim kho cov qib ntawm autophagy-txog cov proteins xws li Beclin-1, VPS34, thiab LC3, txo cov qib ntawm autophagy substrate proteins xws li p62, tab sis tsis cuam tshuam rau qib ntawm lysosomal biogenesis ntsig txog cov proteins xws li ATP61B thiab LAMPV1. Qhov no qhia tau hais tias SS-31 tuaj yeem cuam tshuam rau kev tsim cov autophagosomes tom qab raug mob qaum, xws li p62, tsis muaj kev cuam tshuam rau qib ntawm lysosomal biogenesis ntsig txog cov protein, xws li ATP6V1B2 thiab LAMP1. Qhov no qhia tau hais tias SS-31 tuaj yeem cuam tshuam rau kev tsim cov autophagosomes tom qab kev raug mob ntawm tus txha caj qaum, txhawb kev loj hlob ntawm txoj kev autophagy, pab cov hlwb hauv kev tshem tawm cov khoom puas, thiab rov ua kom muaj kev ruaj ntseg ntawm qhov chaw ntawm lub cev.
Pyroptosis yog ib qho inflammatory programmed necrosis uas ua rau ntau dhau ntawm cellular puas nyob rau hauv ntau yam kab mob. SS-31 txo cov qib ntawm pyroptosis-hais txog cov proteins, xws li ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, thiab IL-18, yog li inhibiting qhov tshwm sim ntawm pyroptosis. Muaj ib qho kev sib cuam tshuam ntawm autophagy thiab pyroptosis; Txhim kho autophagy tuaj yeem inhibit pyroptosis. SS-31 tswj qhov sib npaug no, txo cov cell tuag los ntawm pyroptosis thiab txhawb kev kho cellular thiab ciaj sia.
Daim ntawv thov
Cov Kab Mob Neurological
Kev raug mob ntawm tus txha caj qaum yog ib qho mob loj heev uas ua rau lub cev tsis muaj zog thiab lub cev tsis muaj zog. Vim lub xub ntiag ntawm cov hlab ntsha-hlwb barrier, cov pa tshuaj tawm tsam kom ncav cuag qhov chaw raug mob. SS-31, nrog rau nws lub peev xwm hla cov ntshav-hlwb barrier, qhia tau hais tias muaj peev xwm nyob rau hauv kev kho mob ntawm tus txha caj qaum. Thaum siv los ntawm kev txhaj tshuaj intraperitoneal rau cov nas uas muaj tus txha caj qaum raug mob, kev ntsuam xyuas tus cwj pwm siv BMS nas ntsuas, ntsuas kev taug kev, thiab kev ntsuas dav hlau inclined tau qhia tias nws txhawb nqa kev ua haujlwm zoo tom qab raug mob. Histologically, siv HE, Masson, MAP2, thiab SYN staining, nws tau txiav txim siab tias SS-31 txo qhov chaw ntawm tus txha caj qaum glial caws pliav, nce tus naj npawb ntawm dendrites thiab synapses, thiab txhawb nqa cov txheej txheem thiab kev ua haujlwm ntawm tus txha caj qaum neurons.
Hauv kev tshawb fawb ntawm qee cov kab mob neurodegenerative, xws li Parkinson's disease thiab Alzheimer's disease, SS-31 kuj tau qhia tias muaj peev xwm kho tau tus nqi. Cov kab mob no feem ntau nrog oxidative stress-induced neuronal puas, inflammatory teb, thiab mitochondrial dysfunction. SS-31, los ntawm ntau lub tswv yim xws li tswj hwm mitochondrial muaj nuj nqi, inhibiting inflammatory teb, thiab txhawb cellular autophagy, tuav cov lus cog tseg rau ncua ncua neuronal degeneration thiab txhim kho cov tsos mob ntawm tus neeg mob.
Cov kab mob plawv
Mob plawv tsis ua hauj lwm yog ib qho teeb meem tshwm sim thiab ua rau muaj kev phom sij rau lub neej ntawm sepsis. SS-31 nthuav tawm cov teebmeem tiv thaiv kev raug mob myocardial hauv sepsis. Hauv kev sim vivo, nas nyob hauv SS-31 pab pawg cuam tshuam tau pom zoo txhim kho cov ntaub so ntswg myocardial disorganization thiab inflammatory infiltration piv rau pawg sepsis, thiab txo qis hauv cov hlwb apoptotic. SS-31 tuaj yeem tiv thaiv kev txhim kho ntawm cov kab mob hauv cov ntaub so ntswg myocardial, nce ATP cov ntsiab lus, txhim kho cov xwm txheej redox, tswj cov mitochondrial membrane muaj peev xwm, thiab inhibit qhov ua kom muaj NF-κBp65 thiab NLRP3, yog li txo qis LPS-induced myocardial raug mob. Qhov no qhia tau hais tias SS-31 tuaj yeem dhau los ua cov tshuaj muaj peev xwm los kho sepsis-induced cardiomyopathy.
Hauv lwm cov kab mob plawv, xws li myocardial ischemia-reperfusion raug mob, SS-31 kuj tseem tuaj yeem ua lub luag haujlwm tseem ceeb. Cov txheej txheem myocardial ischemia-reperfusion ua rau kev tsim ntau ntawm ROS, ua rau cov lus teb inflammatory thiab cell apoptosis.
Xaus
SS-31 tuaj yeem nkag mus rau hauv cov ntshav-hlwb teeb meem, lub hom phiaj mitochondria los kho cov cellular puas, thiab muaj peev xwm siv rau hauv cov kab mob neurological, kab mob plawv, kho cov leeg pob txha, thiab mob ntshav qab zib vascular endothelial raug mob. Los ntawm kev tsom mus rau mitochondria raws li lub hom phiaj tseem ceeb, nws muaj txoj kev kho tshiab.
Qhov chaw
[1] Zhu Y, Luo M, Bai X, et al. SS-31, Mitochondria-Targeting Peptide, Ameliorates Raum Kab Mob [J]. Oxidative Medicine thiab Cellular Longevity, 2022,2022:1295509.DOI:10.1155/2022/1295509.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
