Na Cocer Peptides rayt 
am 30 dez bifo
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ di tin dɛn we dɛn dɔn lan
SS-31, we dεn kכl bak Elamipretide, na wan nyu aromatכk kεtyכnik pεptida. SS-31 kin krɔs di blɔd-bren barɛri fri wan, we na wan prɔpati we de mek i fayn fɔ trit nyurolɔjik dizayd. di bכdi-bren barεri de wok lεk implεnt prכtektiv barεri fכ di sεntri nεv sεstem, wit bכku drog dεm de strכg fכ kכros am. כltu, SS-31 de win dis limitεshכn, i de rich di sayt dεm we di nyural dεm dεm dεm dεm dεn dεn de gi op dεm fכ rεpair di nyural sεl dεm we dεn dכn pwεl. i de pan di klas fכ sכm mכlikul pεpti dεm, wit rili lכw mכlikul wet, we de gi am gud mobiliti εn bayoavaylabl insay di bכdi. di kεshכn dεm we SS-31 de kכri de mek i ebul fכ intarakt wit nεgεtiv chaj kכmכpכnεnt dεm na bayolojikal mεmbran dεm, patikyular di nεgεtiv chaj insay mεmbran fכsfolipid dεm na di maytochכndria. dis spεsifi k binding de alaw SS-31 fכ akumulet insay maytochכndria, we de mek in rεgεdyushכn ifekt dεm pan maytochכndria fכnshכn.
Figure 1 Mekanism fכ akshכn fכ SS-31 εgεst kidni sik.
Mekanism fɔ Akshɔn
Rεgulεshכn כf di Maytochכndrial Fכnshכn
di maytochכndria dεm, as di sεl in εnεji pawa, de ple imכtant rol fכ di sεl dεm we de liv εn mεtabolism. SS-31, wit in kεtyכnik strכkchכ, kin kכmכt bכku bכku wan insay di nεgεtiv chaj inna mεmbran fכsfolipid dεm na di maytochכndria, we de mek di maytochכndrial rεspireshכn bכku. di maytochכndrial rεspiretכri chen na imכtant path fכ sεlyul εnεji prodakshכn (ATP). SS-31 de optimize di fכnshכn fכ di rilayt protin dεm na di rεspiretכri chen, impruv εlektrכn transpכt efyushכn, we de protεkt ATP sεntesis εn gi sεl dεm wit inof enεji fכ mεnten nכmal fysiolojikal aktiviti dεm lεk sεl divεlכpmεnt, difrεns, εn mεtirial transpכt.
SS-31 de aktibכt di maytochכndrial bayojεnεsis insay nyuron dεm, we de protεkt di jεnereshכn fכ nyu maytochכndria. we di sεl dεm de fεs damej כ strεs, di jεnereshכn fכ nyu maytochכndria de εp fכ fulכp di maytochכndria dεm we dεn dכn pwεl כ we nכ de wok fayn, we de mεnten di hεlth fכ di maytochכndria populeshכn insay di sεl. i de εnhans di maytochכndrial כtofagi bak, di sεl mεkanism fכ klia di maytochכndria dεm we dεn dכn pwεl. if dεn nכ kכl di maytochכndria dεm we dεn dכn kliya kwik kwik wan, dεn de rilis bכku rεaktiv כksijεn spεshal (ROS), we de damej di sεl dεm mכr. SS-31 de ridyus ROS prodakshכn fayn fayn wan bay we i de εnhans di maytochכndrial כtofagi, we de protεkt sεl dεm frכm כksidεtiv strεs dεmεj.
Inhibiting inflammatory rispכns dεm
insay plεnti sεl dεm we de pwεl, di inflammatory rεspכns dεm kin kכmכt wit di damej. Saytoplasmik fכsfolaypez A2 (cPLA2), as di praymar mεdiεta fכ nyuroinflameshכn, de brok dכn mεmbran fכsfolipid dεm na di sn-2 posishכn fכ laysosom dεm כnda patכlayz kכndishכn dεm, we de prodyuz laysofosfolipid dεm εn ω3 polyunsaturated fεt asid dεm, we de lid to laysosomal mεmbran pεrmiabilizεshכn (LMP) εn mek wan inflammatory envayroment. SS-31 kin dכwnrεgul di εksprεshכn lεvεl fכ fכsfכraylet saytoplasmik fכsfolaypas A2 (p-cPLA2), inhεbit di fכsfכrayleshכn fכ cPLA2, we de ridyus di prodyushכn fכ inflammatory mεdiate dεm εn i de εliviet di dεmεj we inflammatory rεspכns to sεl dεm de kכz.
insay stכdi dεm pan sepsis-indyus mayokardial injuri, dεn fכnshכn se SS-31 de inhεbit di aktibכshכn fכ NF-κB εn NLRP3, we de impruv di mayokardial inflammatory rεspכns dεm. NF-κB na di kכl rεgεlεt fכ di inflammatory signal path dεm, we NLRP3 na imכtant kכmכpכnt fכ di inflammasome. di aktibכshכn we dεn de mek de mek dεn rilis bכku inflammatory fכktכ dεm, lεk IL-6, IL-1β, εn TNF-α. bay we i de inhεbit di aktibכshכn fכ dεn tu ki fכktכ dεm ya, SS-31 de ridyus di εksprεshכn lεvεl dεm fכ inflammatory fכktכ dεm, i de εliviet inflammatory damej to mayokardial sεl dεm, εn de mεnten dεn nכmal fכnshכn.
Promot כtofagi εn inhεbit payroptosis
כtofagi na imכtant mεkanism we de protεkt insεf insay di sεl dεm we de klin di כgan dεm we dεn dכn pwεl, di protin dεm we dεn fold fayn, εn כda tin dεm we de du bad. insay stכdi dεm we dεn du pan spεnal kכd injuri, dεn fכnshכn se SS-31 de εnhans di lεvεl dεm fכ כtofagi-rεlatεd protin dεm lεk Beclin-1, VPS34, εn LC3, de ridyus di lεvεl dεm fכ כtofagi sabstεrayt protin dεm lεk p62, bכt i nכ de afekt di lεvεl dεm fכ di laysosomal bayojεnεsis-rεlatεd protin dεm lεk ATP6V1B2 εn LAMP1. dis sho se SS-31 kin infכlכw di fכmeshכn fכ כtofagכsכm dεm afta spεnal kכd injuri, lεk p62, we nכ de afekt di lεvεl dεm fכ di laysosom bayojεnεsis-rεlatεd protin dεm, lεk ATP6V1B2 εn LAMP1. dis sho se SS-31 kin infכlכw di fכmeshכn fכ כtofagכsכm dεm afta spεnal kכd injuri, protεkt di nכmal prכgreshכn fכ di כtofagi path, εp sεl dεm fכ klia kכmכpכnεnt dεm we dεn dכn, εn rεstכr di stεbiliti fכ di intasεlulyar invayroment.
Payroptosis na inflammatory programmed necrosis we de mek di sεl dεm dεm we de pwεl pasmak pan difrεn sik dεm. SS-31 de ridyus di lεvεl dεm fכ di protin dεm we rilayt fכ payroptosis, lεk ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, εn IL-18, we de mek di payroptosis nכ de apin. wan komplex intaplay de bitwin כtofagi εn payroptosis; εnhans כtofagi kin inhεbit payroptosis. SS-31 de rεgεl dis bεlε, i de ridyus di sεl dεm we de day we di payroptosis de kכz fayn fayn wan εn i de mek di sεl dεm ripa εn sכvayv.
Aplikeshɔn dɛn
Nyurolɔjik Sik dɛn
di spεnal kכd injuri na wan siriכs disabled kכndyushכn we de mek i de lכs fכ fכm fכ כltεm εn mכtalman in mכtalman de impεryus. Bikɔs di blɔd ɛn bren barɛri de, kɔmɔn mɛrɛsin dɛn kin tray tranga wan fɔ rich usay di pɔsin wund. SS-31, wit in abiliti fכ kכros di bכdi-bren barεri, sho prכmis pכtεnshal fכ trit spεnal kכd injuri. we dεn administret via intraperitoneal injεkshכn to mays wit spεnal kכd injuri, bihayvכral asesmεnt we yuz di BMS maws skel, gait analisis, εn inklin plen tεst rεvεl se i sכmtεm protεkt fכnshכnal rεkכvri pכst-injuri. histכlכjik wan, we dεn yuz HE, Masson, MAP2, εn SYN stεyning, dεn dεtermin se SS-31 de ridyus di εria fכ di spεnal kכd glial ska, i de inkrεs di nכmba fכ di dεndrit dεm εn sinaps dεm, εn i de promuot di strכkchכral εn fכnshכnal ripa fכ di spεnal kכd nyuron dεm.
Insay stכdi dεm pan sכm nyurodijεnεraytiv sik dεm, lεk Pakinsin sik εn Alzaima, SS-31 dεn sho bak pɔtεnshal valyu fכ tritmεnt. bכku tεm dεn sik ya kin kam wit כksidεtiv strεs-indyus nyuronal dεmεj, inflammatory rεspכns, εn mitochondrial dysfunction. SS-31, tru mכltipכl mεkanism dεm lεk fכ rεgεl di maytochכndrial fכnshכn, fכ inhεbit inflammatory rεspכns dεm, εn fכ promuot sεlyul כtofagi, de hכl prכmis fכ delay nyuronal dεjεnεreshכn εn impruv di sikman sεmtכm dεm.
Di sik dɛn we kin kam pan pɔsin in at ɛn di blɔd
di kadyak disfכnkshכn na wan kכmכn εn layf-threatεnt kכmplikεshכn fכ sεpsis. SS-31 de sho protεktiv ifekt dεm εgεst mayokardial injuri insay sεpsis. In in vivo εkspεriεns, mays in di SS-31 intavεnshכn grup sho signifyant improv mayokardial tisu disכganayzeshn εn inflammatory infiltrashכn kכmpεr to di sεpsis grup, εn sכm sכm rεdukshכn in apoptotik sεl dεm. SS-31 kin inhεbit di upregulashכn fכ inflammatory fכktכ dεm na di mayokardial tisu, inkrεs ATP kכntεnt, impruv rεdכks stetכs, mεnten di maytochכndrial mεmbran pכtεnshal, εn inhεbit di aktibכshכn fכ NF-κBp65 εn NLRP3, we de mek i εliviet di LPS-indyus mayokardial injuri. dis sho se SS-31 kin bi wan pכtεnshal drog fכ trit sepsis-induced cardiomyopathy.
pan כda sik dεm we de kכmכt na di at, lεk mayokardial ischemia-reperfusion injury, SS-31 kin ple imכtant rol bak. di mayokardial ischemia-riperfyushכn prכsεs de lid to di prodyushכn fכ bכku ROS, we de trigεr inflammatory rεspכns dεm εn sεl apoptosis.
Dɔn
SS-31 kin go insay di bכdi-bren barεri, tכgεt maytochכndria fכ ripεr di sεl dεm we dεn dכn pwεl, εn i gεt pכtεnshal aplikεshכn insay nyurolכjik sik dεm, kכdivaskyul sik dεm, skel mכsul rεpa, εn dayabεtik vaskulεr εndoteyl injuri. bay we i de tכk bכt di maytochכndria as di kכr tכgεt, i de gi nyu tεrapi tiori.
Sos dɛn we dɛn pul
[1] Zhu Y, Luo M, Bai X, ɛn ɔda pipul dɛn. SS-31, we na Maytochondria-Target Pεptid, de Amelioret Kidni Disiz[J]. Oksidativ Mεdisin εn Sεlyul Lכngεviti, 2022,2022:1295509.DOI:10.1155/2022/1295509.
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