SS31 50mg we yu de yuz

▎ SS-31 Struktrɔ

▎ SS-31 Risach

Wetin na di risach bakgrɔn fɔ SS-31?

di risεch bakgrכn fכ SS-31 kכmכt frכm dip כndastandin fכ maytochכndrial disfכnkshכn εn di limitεshכn dεm fכ di tεrapi aprכch dεm we de naw. di maytochכndria dεm na imכtant fכ di sεl dεm we de wok εn fכ wok, εn di disfכnkshכn we dεn nכ de wok de sho se difrεn sik dεm de bigin εn go bifo, lεk kidni sik, nyurodijεnεraytiv dizכrd, εn at fεil. insay dεn kכndishכn dεm ya, abnכmaliti dεm na di maytochכndrial bayojεnεsis, mכfכlכji, fכnshכn, εn dinamik chenj dεm de kכmכt, we de mek maytochכndria bi krichכl tεrapi tכgεt. pan ɔl we sɔm maytochondrial-targeted drɔgs de—inklud NAD+ suplimɛnt dɛn lɛk nicotinamide mononucleotide (NMN), di mitochondrial-targeted protective compound MitoQ, ɛn di antioxidant coenzyme Q10—tradishɔnal mɛrɛsin dɛn de gɛt klinik limiteshɔn bikɔs ɔf di po mitochondrial upteke ɔ ay toksisiti. Fɔseka dat, nid de fɔ mek dɛn mek mɔ tritmɛnt dɛn we go wok fayn ɛn we dɛn go tɔk to dɛn.

strεs-indyus at fεil de riprizent wan pan di praymar kכz dεm fכ at fεil na di gכl, wit in pathophysiology we kכl kכlכs to mitochondrial dysfunction εn myocardial interstitial fibrosis. Fɔ no di fayn fayn we dɛn fɔ mɛn pipul dɛn na impɔtant tin fɔ mek di sikman in autkam bɛtɛ. Agens dis bakdrop, risechar dεm divεlכp SS-31, wan nכvel mitochondrial-targeted antioxidant, fכ adrεs di tεrapi nid fכ mitochondrial dysfunction-related diseases. i de akt spεshal wan pan di insay maytochכndrial mεmbran, we de stεbyul di maytochכndrial strכkchכ εn fכnshכn we i de ridyus כksidεtiv strεs, we de sho efficacy in mכltipכl sik mכdel dεm.

Wetin na di we aw SS-31 de wok?

rεgulεt di mitochondrial mεmbran fכnshכn

intarakshכn wit di kכdiolipin: di εlamipretide de kכros di כta maytochכndrial mεmbran εn i de tay to di kכdiolipin. di kכdiolipin na di kכl fכsfolipid kכmכpכnt fכ di insay maytochכndrial mεmbran, we de ple imכtant rol fכ mεnten di maytochכndrial strכkchכ εn fכnshכn. tru dis intarakshכn, Elamipretide de impruv di maytochכndrial bayoεnεjεtiks εn mכfכlכji. dis prכsεs de sho lεk rεpid εnhansmεnt fכ di maytochכndrial fכnshכn insay indyuz pluripotεnt stεm sεl dεm, patikyular in sεl dεm we kכmכt frכm pasεnshכn wit Barth sεndrכm εn כda inhεrit pikin dεm kכdiכmayopathies ^[1]..

כltεr di mεmbran fכs prכpati dεm: Mitchell W in risεch sho se Elamipretide de intarakt wit di lipid bilayεr, we de mכdify di fכs prכpati dεm fכ di maytochכndrial mεmbran, patikyular di ilektrostatik prכpati dεm na di mεmbran intafεys. dis pεptida de distribyut to di mεmbran intafεys rijyכn wit afiniti εn binding dεnsiti we dεn kכrεlat dεn wan wit sכfayz chכj. pan tap we i nכ de dεstabiliz di lamellar bilayer pan hכy binding kכnsantreshכn, i de indyuz satεrayshכn chenj dεm na lipid stεk, we de afekt di maytochכndrial mεmbran fכnshכn ^{[2] .}.

Figure 1 Factor dεm we de afekt di kadyak enεji saplai εn dimand ^[1]..

Fɔ protɛkt di Nɛvɔs Sistɛm

Enhancing Cognitive Function: Insay wan lipopolysaccharide (LPS)-induced mouse model of memory impairment, Elamipretide tritmεnt sכmtεm impruv lanin εn mεmכri abiliti dεm na di Morris wata maze (MWM) εn kondishכn ples fכ fred tεst dεm. dis ameliorative ifekt kin bi asכsiet wit in protεkshכn fכ di maytochכndrial fכnshכn, rεdukshכn fכ כksidεtiv strεs, rεguleshכn fכ di bren-dεriv nyurotrofik fכktכ (BDNF) signal path, εn εnhansmεnt fכ di sinaptik strכkchכral kכmplisiti. LPS tritmεnt indyuz maytochכndrial disfכnkshכn, כksidεtiv strεs, inflameshכn, nyuronal apoptosis, εn dεndritik spayna lכs in di maws hipokamp, ​​we Elamipretide mitigate dεn injuri ya, we sho pכtεnshal fכ prεvεnt periכpεraytiv nyurokognitiv disfכnkshכn (PND) ^[3]..

inhibishכn fכ Nyuronal Apoptosis: insay spεnal kכd injuri (SCI) stכdi dεm, Elamipretide de promuot fכnshכnal rεkכvεshכn bay we i de sכpres di payroptosis, εnhans כtofagi, εn ridyus laysosomal mεmbran pεrmiabiliti (LMP). i de εnhans כtofagi bay we i de inhεbit cPLA2 fכsfכrayleshכn we i de mitigate payroptosis εn LMP. כl dis de sho se Elamipretide de ple imכtant rol fכ ripa nyurolכjik injuri dεm bay we i de rεgεl mכltipכl sεlyul prכsεs dεm, ridyus nyuronal apoptosis, εn protεkt nyural fכnshכnal rεkכvεshכn ^[4]..

Figure 2 Elamipretide (SS-31) atenuated oksidativ strεs εn di inflammatory rεspכns we LPS indyuz insay di maws hipokampus. a Riaktiv כksijεn spεshal (ROS) lεvεl dεm, b malondialdehyde (MDA) lεvεl dεm, εn c supεrכksayd dismutase (SOD) aktiviti dεm ^{[3] .}.

Wetin na di aplikeshɔn dɛn fɔ SS-31?

Nyurolɔjik Dizayd dɛn

Tritmɛnt fɔ Traumatik Ɔptik Nyuropati: Traumatik ɔptik nyuropati (TON) kin mek pɔsin nɔ de si fayn fɔ ɔltɛm bikɔs ɔf blunt ɔrbital trauma. stכdi dεn dכn invεstigat di nyuroprotεktiv ifekt dεm we SS-31 kכmbayn wit di tכmכro nεkrכsis fכktכ (TNF) inhibito etanercept pan rεtina ganglion sεl dεm (RGCs) fכlכ optik nεv injuri. Tse BC in stכdi we yuz wan maws ultrasound-indyus TON mכdel (SI-TON) fכnכt se intravitreal injεkshכn fכ SS-31 kכmbayn wit sabkutan injεkshכn fכ etanercept εn SS-31 sכmtεm inkrεs RGC sכvayvεns bay 21% (p < 0.01) kכmpεr to fכsfεt-bכfa salin (PBS)-trit kכntrכl yay. Kombayn sabkutan injεkshכn fכ etanercept εn SS-31 inkrεs RGC sכvayvεns bay 11% (p < 0.05) kכmpεr to kכntrol; sכbkutan injεkshכn fכ etanercept nכmכ inkrεs RGC sכvayvεns bay 20% (p < 0.01) kכmpεr to kכntrol dεm; Sabkutan injεkshכn fכ SS-31 nכmכ inkrεs RGC sכvayvεns bay 17% kכmpεr to di kכntrol grup (p < 0.01). dis fכnd dεm sho se SS-31 de εksyεrt wan prכtektiv ifekt pan RGC dεm fכ trit traumatik optik nyuropathy, we de impruv di vishכnal akyuiti in TON pasεnshכn dεm ^[5]..

impruvmεnt in α-Synuclein-Rεlatεd Nyurodijεnεraytiv Disizεs: Parkinson in sik εn rilatεd synucleinopathies de kכlכsכl wit di mεmbran binding εn agregεshכn prכpati dεm fכ α-synuclein. Stefaniak in risach kכnfכm se SS-31 kin dכz-dipεndεntli displεs כl tu di wayl-tayp εn N-tεrminal asetεlayt α-synuclein frכm nεgεtiv chaj sכm mכnolayεr vεsikul dεm, inhεbit mεmbran-indyus α-synuclein agregεshכn, εn altεr in fibrilar mכfכlכji. fכ tכk di tru, SS-31 de rεstכr di displεsmεnt fכ di sinuklin frכm nεgεtiv chaj sכm mכnolayεr vεsikul dεm, i de inhεbit mεmbran-indyus α-synuclein agregεshכn, εn i de altεr in fibrila mכfכlכji. apat frכm dat, SS-31 kin rεstכr di displεsmεnt fכ di synuclein - frכm nεgεtiv chaj sכm sכm unilamellar vεsikul dεm, inhεbit mεmbran-indyus α-SNIP agregεshכn, εn altεr in fibrilar mכfכlכji. fכ tכk di tru, SS-31 rεstכr impεriכs maytochכndrial fכnshכn in nyuroblastoma sεl dεm we dεn trit wit α-SNIP oligomεr dεm εn blכk sεlyul כptek fכ dεn oligomεr dεm ya. dis fכndכm dεm de hεlayt SS-31 in mכlti fכs protεktiv ifekt dεm εgεst α-synuclein agregεshכn-indyus mitochondrial disfכnkshכn, we de posishכn am fכ mitigate nyurodijεnεraytiv sik dεm we de aכsכsiayt wit α-synuclein misfolding εn agregεshכn ^[6]..

Domɛyn fɔ sik dɛn we de mek pɔsin in at ɛn di blɔd

Improving Mitochondrial Function in Hat Failure Patients: Dɛn no se bad bad maytochondrial ɔltɛrayshɔn de insay di wan dɛn we gɛt at fεil (HF). stכdi dεm trit fresh ex vivo fεil εn nכn fεylin vεntrikul tisu frכm pikin εn big pipul wit SS-31, mεzj mitochondrial כksijεn fluks, kכmpleks (C)I εn CIV aktvכti, εn jel-bεys aktvכti fכ supakomplεks asembli. di tin dεm we Chatfield fכnshכn sho se di maytochכndrial fכnshכn de pwεl pan mכtalman at we de fεl. fכlכ SS-31 tritmεnt, di maytochכndrial כksijεn fכlכ, CI εn CIV aktvכti, εn CIV aktvכti we riliyt to supεrkomplεks assembly sכmtεm impruv, we sho se SS-31 de εnhans di maytochכndrial fכnshכn fayn fayn wan insay mכtalman at we de fεl εn i kin intavεn insay at fεil ^[7]..

Tritmɛnt fɔ Barth Syndrome Cardiomyopathy: Barth syndrome na wan sik we nɔ kin apin so ɔltɛm ɛn we kin kil X-linked disɔda we de sho se pikin dɛn kin day bɔku ɛn i kin go bifo to kadiomayopathy wit siriɔs imyun sistɛm we nɔ de wok fayn. SS-31 na wata-sכlubul, aromatכk kεtyכnik, maytochכndrial-tכgεt tεtrapεptida we de rεdi fכ pεnεtrayt εn transiεntli lokaliz to di insay maytochכndrial mεmbran. i de protεkt sεlyul hεlth εn i de mek כksidεtiv strεs bכku bay we i de εnhans εnεji prodakshכn εn sכpres fכmeshכn we di rεaktiv כksijεn spεs dεm we pasmak. Sabbah risach sho se SS-31 de impruv mitochondrial bioenergetics εn mכfכlכji kwik kwik wan insay indyuz pluripotεnt stεm sεl dεm we kכmכt frכm pasεnshכn dεm wit Barth sεndrכm. Data frɔm bɔku sik mɔdel dɛn sho se SS-31 gɛt prɔmis as pɔtɛnɛshɛl tɛrapi fɔ pasɛnt dɛn we gɛt Barth syndrome cardiomyopathy, we de sho patikyula pronɔns ifɛkt pan di wan dɛn we dɛn no se gɛt kadiomayopathy. i kin εksyεrt wan las impak pan di kכdiכmayopati prכgreshכn we i de sכmtεm strכkchכral rivεs di rεmכdelin fכ fεil lεft vεntrikl dεm na di gכlכbal, sεlyul, εn mכlikul lεvεl dεm ^[1]. .

Musculoskeletal Disease Domain: Dɛn sho se dɛn gɛt tritmɛnt pɔtɛnɛshɔn na tendinopathy. Zhang X in stכdi yuz wan maws supraspinatus tendinopathy mכdel, we divayd 126 mays (252 limb) insay siks εkspεriεns grup dεm. di rizulεt frכm Zhang X sho se di tεndon rכpchכ fכs dכn dכn pכst-impakt kכmpεr to intakt tεndon dεm. Dis ridyushɔn bin patli rivεs afta dɛn pul di klem, SS-31 tritmɛnt, ɔ kɔmbayn tɛrapi, wit stiffnɛs we de sho wan sem kayn patɛn. Histolojikal analisis rivεl hכy modifyed Bonar skכ dεm na di impak grup, we kכmbayn tεrapi patli rivεs mכfכlכjik chenj dεm na di tεndon. di grup we impak sho se di maytochכndrial nכmba dεm dכn rεdכks εn dεn chenj di kristכl כganayzeshn εn dεnsiti. fכlכ di klem rimobul εn/כ SS-31 tritmεnt, di maytochכndrial strכkchכ εn kwantiti nכmal, εn di kristכs mכfכlכji improv. Superoxide dismutase (SOD) aktiviti dεkrεs pכst-impεkt kכmpεr to kכntrol bכt inkrεs sכmtεm afta tritmεnt, patikyular in di kכmbayn tεrapi grup. di maytochכndria-rεlatεd jin εksprεshכn dεkrεs in di impak grup bכt i ribaund afta tritmεnt. dis de sho se SS-31, as di maytochכndrial protεktכ, de impruv di maytochכndrial fכnshכn εn i de protεkt di tεndon hεlin, wit εnhans efikכs we dεn kכmbayn wit subakromial impingεmεnt rεmכval. i de ol positifu tεrapi pכtεnshal fכ supraspinatus tεndinopathy [8].

Dɔn

SS-31 (Elamipretide), as di maytochכndrial-tכgεt tεtrapεptida, de achy mitochondrial fכnshכn protεkshכn εn mכlti-sistεm injuri ripa. i de biεn fכsfatidylserin insay di insay maytochכndrial mεmbran, i de stεbyul di mεmbran strכkchכ εn pכtεnshal, i de εnhans di rεspiretכri chen kכmpleks aktiviti fכ protεkt ATP prodakshכn, εn i de impruv sεlyul εnεji mεtabolism. di sem tεm, i de sכpres εksyכs riaktiv כksijεn spεs (ROS) jεnereshכn, upregulate antioksidant εnzym aktiviti, εn mitigate כksidεtiv strεs dεmεj. we i kam pan inflammatory rεguleshכn, i de inhεbit NF-κB εn NLRP3 inflammasome aktibכshכn, we de ridyus di pro-inflammatory fכktכ rilis. i de mכdulet כtofagi path dεm, sכpres apoptosis, εn de mεnten di maytochכndrial homכstasis tru rilayt path dεm. dis akshכn dεm de gi bεnεfit ifekt dεm na sik dεm we involv maytochכndrial disfכnkshכn akraos di kכdivaskyul, nyurolכjik, εn mכskul skel sistεm dεm.

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Di tin dɛn we wi dɔn tɔk bɔt, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.

Sayɛns Jɔnal Author

Kathryn C. Chatfield na wan risachman na di Yunivasiti ɔf Kolorado Skul fɔ Mɛdisin, we gɛt fɔ du wit di Dipatmɛnt fɔ Pikin ɛn Mɛdisin/Divishɔn fɔ Kadiɔlɔji. I de pe atɛnshɔn pan pikin dɛn kadyolɔji ɛn maytochondrial bayoloji, i de invɛstigat di we aw di at de wok ɛn di sik. I dɔn kɔntribyut bɔku pan di fil tru skɔlaship pɔblikeshɔn ɛn kɔlabɔreshɔn, ɛn dɛn no in wok fɔ advans ɔndastandin bɔt kadiovaskular fisiɔlɔji ɛn pɔtɛnɛshɛl tritmɛnt strateji. Kathryn C. Chatfield de na di list insay di rɛfrɛns fɔ saytayshɔn [7].

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Sabah HN., ɛn ɔda pipul dɛn. Elamipretide fɔ Barth syndrome cardiomyopathy: smɔl smɔl fɔ bil bak wan pawa grid we dɔn fel. Rivyu fɔ At Fayla 2022; 27(5): 1911-1923.DOI: 10.1007/s10741-021-10177-8.

[2] Mitchell W, Ng E. A., Tamucci J. D., ɛn ɔda pipul dɛn. Mכlikul Mεkanism כf Akshכn כf Maytochondrial Tεrapi SS-31 (Elamipretide): Mεmbran Intarakshכn εn Ifεkt pan Surface Ilektrostatiks. Biorxiv 2019. https://api.semanticscholar.org/CorpusID:202016574. Di wan dɛn we de stɔdi bɔt di Baybul.

[3] Zhao W, Xu Z, Cao J, ɛn ɔda pipul dɛn. elamipretide (SS-31) de impruv di maytochכndrial disfכnkshכn, sinaptik εn mεmכri impεryans we lipopolysaccharide indyuz insay mays. J ɔ rnal ɔ f Nyuroinflameshɔn 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, ɛn ɔda pipul dɛn. elamipretide de εliviet payroptosis in traumatikli injured spεnal kכd bay we i de inhεbit cPLA2-indyus laysosomal mεmbran pεrmiabilizεshכn. J ɔ rnal ɔ f Nyuroinflameshɔn 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse B. C., Dvoriantchikova G, Tao W, ɛn ɔda pipul dɛn. Mitochondrial targeted tεrapi wit elamipretide (MTP-131) as adjunkt to tumor nεkrכsis fכktכ inhibishכn fכ traumatik optik nyuropathy in di akyu sεtin. Ekspirimɛnt Ay Risach 2020; 199: 108178.DOI: 10.1016/j.ɛksa.2020.108178.

[6] Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Tεrapi Pεptid SS-31 de Modulεt Mεmbran Binding εn Agregεshכn כf $alpha$-Synuclein εn de Rεstכr Impεyεr Maytochכndrial Fכnshכn. Biorxiv 2024. https://api.semanticscholar.org/CorpusID:271162443. Di wan dɛn we de stɔdi bɔt di Baybul.

[7] Chatfild K. C., Sparagna G. C., Chau S, ɛn ɔda pipul dɛn. Elamipretide de impruv di maytochondrial fכnshכn na di fεil mכtalman at. Jacc-Basic to Transleshɔnal Sayns 2019; 4(2): 147-157.DOI: 10.1016/j.jacbts.2018.12.005.

[8] Zhang X, Bowen E, Zhang M, Szeto HH, Deng XH, Rodeo S. A., ɛn ɔda pipul dɛn. SS-31 as wan Maytochondrial Protektant in di Tritmεnt כf Tεndinopathy: Evalueshכn in wan Murine Supraspinatus Tεndinopathy Mכdel. Jɔnal fɔ Bɔn ɛn Jɔyn Sɔjri-Amɛrikan Volyum 2022; 104 (21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

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 famasitik, 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.