Cocer Peptides ye ŋlɔe 
ŋkeke 30 enye sia
NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.
Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.
Kpɔɖeŋu bliboa
SS-31, si wogayɔna be Elamipretide, nye cationic peptide ʋeʋĩ yeye aɖe. SS-31 ate ŋu atso ʋu kple ahɔhɔ̃ ƒe mɔxenu faa, si nye nɔnɔme si na wòsɔ na ahɔhɔ̃mekawo ƒe dɔlélewo dada. Ʋu kple ahɔhɔ̃ ƒe mɔxenu nyea mɔxenu vevi aɖe si kpɔa lãmekawo ta, eye atike akpa gãtɔ ʋlina vevie be yewoatsoe. Gake SS-31 ɖua seɖoƒe sia dzi, eye wòɖoa afisi ahɔhɔ̃mekawo gblẽ le tẽ eye wònaa mɔkpɔkpɔ be woaɖɔ ahɔhɔ̃mekawo ƒe lãmenugbagbeviwo ƒe gbegblẽ ɖo. Enɔ peptide siwo me molecule suewo le ƒe hatsotso me, eye woƒe molecule ƒe kpekpeme le sue vie, si na wòte ŋu ʋãna nyuie eye wòte ŋu nɔa agbe le ŋutilãa me. Cation siwo SS-31 tsɔna na wòte ŋu wɔa dɔ kple nugbagbeviwo ƒe lãkusiwo ƒe akpa siwo me dzoxɔxɔ gbegblẽ le, vevietɔ mitochondria ƒe lãkusi ememe phospholipids siwo me dzoxɔxɔ gbegblẽ le. Kadodo sia koŋ nana SS-31 ƒoa ƒu ɖe mitochondria me, si wɔnɛ be eƒe ɖoɖowɔwɔ ƒe ŋusẽkpɔɖeamedziwo wɔa dɔ ɖe mitochondria ƒe dɔwɔwɔ dzi.
Nɔnɔmetata 1 Mɔnu si dzi SS-31 wɔna ɖe ayikudɔ ŋu.
Dɔwɔwɔ ƒe Mɔnu
Mitochondrial ƒe Dɔwɔwɔ ƒe Ðoɖowɔwɔ
Mitochondria, abe lãmenugbagbevi ƒe ŋusẽŋusẽ ene, wɔa akpa vevi aɖe le lãmenugbagbeviwo ƒe agbenɔnɔ kple woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me. SS-31, kple eƒe cationic wɔwɔme, ate ŋu aƒo ƒu ɖe mitochondria ƒe ememe lãkusi me phospholipids siwo me dzoxɔxɔ gbegblẽ le me geɖe, si ana mitochondria ƒe gbɔgbɔ nanyo ɖe edzi. Mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔ nye mɔ vevi aɖe si dzi woato awɔ lãmenugbagbeviwo ƒe ŋusẽ (ATP). SS-31 naa protein siwo do ƒome kplii ƒe dɔwɔwɔ nyuie wu le gbɔgbɔtsixe ƒe kɔsɔkɔsɔa me, si wɔnɛ be elektrɔnikwo ƒe tsɔtsɔ yi teƒe bubuwo nyona ɖe edzi, si wɔnɛ be wòdoa ATP ƒe wɔwɔ ɖe ŋgɔ eye wònaa ŋusẽ si sɔ lãmenugbagbeviwo be woalé ŋutilã ƒe dɔwɔwɔ siwo sɔ abe lãmenugbagbeviwo ƒe mama, vovototodedeameme, kple nuwo tsɔtsɔ yi teƒe bubuwo ene me ɖe asi.
SS-31 naa mitochondria biogenesis wɔa dɔ le ahɔhɔ̃mekawo me, si doa mitochondria yeyewo ƒe dzidzi ɖe ŋgɔ. Ne lãmenugbagbeviwo dze ŋgɔ nusiwo gblẽ alo nuteɖeamedzi la, mitochondria yeyewo dzidzi kpena ɖe mitochondria siwo gblẽ alo esiwo mewɔa dɔ nyuie o la gbugbɔgaɖoa ŋu, si wɔnɛ be mitochondria siwo le lãmenugbagbevi la me ƒe lãmesẽ nɔa anyi. Edoa ŋusẽ mitochondrial autophagy, si nye lãmenugbagbeviwo ƒe mɔnu si wotsɔ kɔa mitochondria siwo gblẽ la hã ŋudɔ. Ne womeɖe mitochondria siwo gblẽ la ɖa enumake o la, woɖea oxygen ƒomevi siwo wɔa dɔ (ROS) gbogbo aɖewo ɖe go, si gagblẽa nu le lãmenugbagbeviwo ŋu geɖe wu. SS-31 ɖea ROS wɔwɔ dzi kpɔtɔna nyuie to mitochondrial autophagy dzi ɖeɖe kpɔtɔ me, si wɔnɛ be ekpɔa lãmenugbagbeviwo ta tso oxidative stress ƒe nugbegblẽ me.
Mɔxexe ɖe dɔdzẽ ƒe ŋuɖoɖowo nu
Le lãmenugbagbeviwo ƒe gbegblẽ ƒe ɖoɖo geɖe me la, zi geɖe la, dɔdzẽ ƒe ŋuɖoɖowo kpena ɖe nusiwo gblẽ ŋu. Cytoplasmic phospholipase A2 (cPLA2), abe domenɔla vevitɔ na ahɔhɔ̃mekawo ƒe dɔdzẽ ene, gblẽa membrane phospholipids le lysosomes ƒe sn-2 nɔƒe le dɔléle ƒe nɔnɔmewo me, si wɔa lysophospholipids kple ω3 polyunsaturated fatty acids, si hea lysosomal membrane permeabilization (LMP) vɛ eye wòwɔa dɔdzẽ ƒe nɔnɔme. SS-31 ate ŋu aɖe phosphorylated cytoplasmic phospholipase A2 (p-cPLA2) ƒe ɖeɖefia ƒe agbɔsɔsɔ dzi akpɔtɔ, axe mɔ ɖe cPLA2 ƒe phosphorylation nu, si ana wòaɖe dɔdzẽ ƒe domenɔlawo ƒe wɔwɔ dzi akpɔtɔ eye wòaɖe nusiwo dɔdzẽ ƒe ŋuɖoɖo ɖe lãmenugbagbeviwo ŋu hena vɛ dzi akpɔtɔ.
Le numekuku siwo wowɔ tso dzitodzito me abi si dɔlékuiwutikewo hena vɛ ŋu me la, wokpɔe be SS-31 xea mɔ na NF-κB kple NLRP3 ƒe dɔwɔwɔ, si wɔnɛ be dzitodzito me dɔdzẽ ƒe ŋuɖoɖowo nyona ɖe edzi. NF-κB nye dɔdzẽ ƒe dzesimɔwo dzi kpɔla vevi aɖe, evɔ NLRP3 ya nye dɔdzẽ ƒe akpa vevi aɖe. Woƒe dɔwɔwɔ nana be dɔdzẽ ƒe nu gbogbo aɖewo abe IL-6, IL-1β, kple TNF-α ene dona. To mɔxexe ɖe nu vevi eve siawo ƒe dɔwɔwɔ nu me la, SS-31 ɖea dɔdzẽ ƒe nusiwo woɖena fiana ƒe agbɔsɔsɔ dzi kpɔtɔna, eɖea dɔdzẽ ƒe nugbegblẽ le dzitodzito me lãmenugbagbeviwo ŋu dzi kpɔtɔna, eye wòléa woƒe dɔwɔwɔ nyuie me ɖe asi.
Autophagy dodo ɖe ŋgɔ kple mɔxexe ɖe pyroptosis nu
Autophagy nye mɔnu vevi aɖe si kpɔa eɖokui ta le lãmenugbagbeviwo me si kɔa ŋutinu siwo gblẽ, protein siwo womebla nyuie o, kple nu bubu siwo gblẽa nu le ame ŋu la ɖa. Le numekuku siwo wowɔ tso aklã ƒe abixɔxɔ ŋu me la, wokpɔe be SS-31 doa protein siwo do ƒome kple autophagy abe Beclin-1, VPS34, kple LC3 ƒe agbɔsɔsɔ ɖe ŋgɔ, eɖea autophagy substrate proteins abe p62 ene ƒe agbɔsɔsɔ dzi kpɔtɔna, gake mekpɔa ŋusẽ ɖe protein siwo do ƒome kple lysosomal biogenesis abe ATP6V1B2 kple LAMP1 ƒe agbɔsɔsɔ dzi o. Esia ɖee fia be SS-31 ate ŋu akpɔ ŋusẽ ɖe autophagosomes ƒe wɔwɔme dzi le aklã ƒe abixɔxɔ megbe, abe p62 ene, evɔ makpɔ ŋusẽ ɖe protein siwo do ƒome kple lysosomal biogenesis, abe ATP6V1B2 kple LAMP1 ene ƒe agbɔsɔsɔ dzi o. Esia fia be SS-31 ate ŋu akpɔ ŋusẽ ɖe autophagosomes ƒe wɔwɔme dzi le abixɔxɔ le aklã me megbe, ado autophagy mɔa ƒe ŋgɔyiyi si sɔ ɖe ŋgɔ, akpe ɖe lãmenugbagbeviwo ŋu be woaɖe akpa siwo gblẽ la ɖa, eye wòana lãmenugbagbeviwo me ƒe nɔnɔme nagali ke.
Pyroptosis nye dɔdzẽ ƒe ɖoɖowɔɖi ƒe necrosis si hea lãmenugbagbeviwo ƒe gbegblẽ fũu akpa le dɔléle vovovowo me. SS-31 ɖea protein siwo do ƒome kple pyroptosis, abe ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, kple IL-18 ene ƒe agbɔsɔsɔ dzi kpɔtɔna, si wɔnɛ be wòxea mɔ na pyroptosis ƒe dzɔdzɔ. Kadodo sesẽ aɖe le autophagy kple pyroptosis dome; autophagy si doa ŋusẽ ame ate ŋu axe mɔ ɖe pyroptosis nu. SS-31 ɖɔa dadasɔ sia ɖo, si ɖea lãmenugbagbeviwo ƒe kuku si pyroptosis hena vɛ dzi kpɔtɔna nyuie eye wòdoa lãmenugbagbeviwo ɖɔɖɔɖo kple agbetsitsi ɖe ŋgɔ.
Dɔbiagbalẽviwo
Ahɔhɔ̃mekawo ƒe Dɔlélewo
Abi si woxɔna le aklã me nye nuwɔametɔnyenye sesẽ aɖe si hea dɔwɔwɔ ƒe gbegblẽ tegbee kple eƒe dɔwɔwɔ ƒe dɔmawɔmawɔ nyuie vɛ. Le ʋu kple ahɔhɔ̃ ƒe mɔxenu ƒe anyinɔnɔ ta la, atike siwo wozãna ɖaa la ʋlina vevie be yewoaɖo afisi woxɔ abi le. SS-31, kple ŋutete si le esi be wòatso ʋu kple ahɔhɔ̃ ƒe mɔxenu la ɖe ŋutete si ŋugbe wodo fia le aklã ƒe abi dada me. Ne wodoe to dɔgbo me dodo na sisiblisi siwo xɔ abi le aklã me la, nuwɔna ŋuti numekuku siwo wowɔ to BMS sisiblisi ƒe dzidzenu, azɔlizɔzɔ me dzodzro, kple yameʋu ƒe dodokpɔ si me woɖea afɔ le zazã me ɖee fia be edoa dɔwɔwɔ ƒe hayahaya ɖe ŋgɔ ŋutɔ le abixɔxɔ megbe. Le lãmenugbagbeviwo ŋuti nunya gome la, wozã HE, Masson, MAP2, kple SYN ƒe amadede tsɔ kpɔe be SS-31 ɖea afisi aklã ƒe glial scarring le dzi kpɔtɔna, edzia dendrites kple synapses ƒe xexlẽme ɖe edzi, eye wòdoa aklã ƒe ahɔhɔ̃mekawo ƒe wɔwɔme kple dɔwɔwɔ ɖɔɖɔɖo ɖe ŋgɔ.
Le numekuku siwo wowɔ tso ahɔhɔ̃mekawo ƒe dɔléle aɖewo abe Parkinson ƒe dɔléle kple Alzheimer ƒe dɔléle ene ŋu me la, SS-31 hã ɖee fia be viɖe ate ŋu anɔ eŋu le atikewɔwɔ me. Zi geɖe la, ahɔhɔ̃mekawo ƒe gbegblẽ si oxidative stress hena vɛ, dɔdzẽ ƒe ŋuɖoɖo, kple mitochondria ƒe dɔmawɔmawɔ nyuie kpena ɖe dɔléle siawo ŋu. SS-31, to mɔnu vovovowo abe mitochondria ƒe dɔwɔwɔ dzi kpɔkpɔ, mɔxexe ɖe dɔdzẽ ƒe ŋuɖoɖowo nu, kple lãmenugbagbeviwo ƒe autophagy dodo ɖe ŋgɔ ene dzi la do ŋugbe be yeahe ahɔhɔ̃mekawo ƒe gbegblẽ ɖe megbe eye yeana dɔnɔwo ƒe dzesiwo nanyo ɖe edzi.
Dzitodzito me Dɔlélewo
Dzi ƒe dɔmawɔmawɔ nyuie nye kuxi si bɔ eye wòdea ame ƒe agbe afɔku me le dɔlékuiwutikewo ƒe dɔlékuiwutikewo me. SS-31 ɖea ametakpɔkpɔ ƒe ŋusẽkpɔɖeamedzi fiana tso dzitodzito ƒe abixɔxɔ le dɔlékuiwutikewo me. Le dodokpɔ siwo wowɔ le vivo me la, mice siwo le SS-31 ƒe nudede nyawo me ƒe ƒuƒoƒoa me ɖee fia be dzitodzito me lãkusiwo ƒe ɖoɖomawɔmawɔ kple dɔdzẽ ƒe gege ɖe lãme na wo nyo ɖe edzi ŋutɔ ne wotsɔe sɔ kple sepsis ƒuƒoƒoa, eye woɖe apoptotic cells dzi kpɔtɔ ŋutɔ. SS-31 ate ŋu axe mɔ ɖe dɔdzẽ ƒe nusiwo le dzitodzito me ƒe dziyiyi nu, ana ATP ƒe agbɔsɔsɔ nadzi ɖe edzi, ana redox ƒe nɔnɔme nanyo ɖe edzi, alé mitochondrial membrane ƒe ŋutete me ɖe asi, eye wòaxe mɔ na NF-κBp65 kple NLRP3 ƒe dɔwɔwɔ, si ana dzitodzito me abi si LPS hena vɛ dzi naɖe akpɔtɔ. Esia fia be SS-31 ate ŋu ava zu atike si woate ŋu azã atsɔ ada dzitodzito me dɔléle si dɔlékuiwutikewo hena vɛ.
Le dzitodzito me dɔléle bubuwo abe dzitodzito me ʋu ƒe sisi-gbugbɔgaʋu ƒe abi ene me la, SS-31 ate ŋu awɔ akpa vevi aɖe hã. Dzitodzito me ʋu ƒe sisi-gbugbɔ ʋudodo ƒe ɖoɖoa hea ROS gbogbo aɖe vɛ, si hea dɔdzẽ ƒe ŋuɖoɖowo kple lãmenugbagbeviwo ƒe tsɔtsrɔ̃ vɛ.
Nyanuwuwuw
SS-31 ate ŋu age ɖe ʋu kple ahɔhɔ̃ ƒe mɔxenu me, aɖo taɖodzinu na mitochondria be wòaɖɔ lãmenugbagbeviwo ƒe gbegblẽ ɖo, eye woate ŋu azãe le ahɔhɔ̃medɔlélewo, dzitodzito me dɔlélewo, ƒunukpeƒeŋusẽwo ɖɔɖɔɖo, kple suklidɔ ƒe ʋukawo ƒe abixɔxɔ me. Esi wòɖo taɖodzinu na mitochondria be eyae nye taɖodzinu vevitɔ ta la, enaa atikewɔwɔ ŋuti nufiafia yeye aɖe.
Dzɔtsoƒewo
[1] Zhu Y, Luo M, Bai X, kple ame bubuwo. SS-31, si nye Mitochondria-Targeting Peptide, Ðea Ayikudɔléle Dzi Ðe Edzi[J]. Oxidative Atikewɔwɔ kple Lãmenugbagbeviwo ƒe Agbenɔƒe Didi, 2022,2022:1295509.DOI:10.1155/2022/1295509.
Adzɔnu si li na numekuku zazã ɖeɖeko:
