SS31 50mg

▎ Imiterere ya SS-31

SS SS-31 Ubushakashatsi

Ni ubuhe bushakashatsi bwakozwe na SS-31?

Ubushakashatsi bwibanze bwa SS-31 buturuka ku gusobanukirwa byimbitse ku mikorere mibi ya mitochondial nimbogamizi zuburyo bwo kuvura buriho. Mitochondria ni ingenzi cyane mu bikorwa bya selile no mu mikorere, kandi imikorere idahwitse ifitanye isano no gutangira no gutera imbere kwindwara zitandukanye, nk'indwara zimpyiko, indwara zifata ubwonko, ndetse no kunanirwa k'umutima. Muri ibi bihe, ibintu bidasanzwe muri biogenezi ya mitochondial, morphologie, imikorere, nimpinduka zikomeye bigenda bigaragara, bigatuma mitochondriya iba intego ikomeye yo kuvura. Nubwo imiti myinshi yibasiwe na mitochondial ibaho-harimo inyongera ya NAD + nka nicotinamide mononucleotide (NMN), imiti igabanya ubukana bwa mitochondrial MitoQ, hamwe na antioxydeant coenzyme Q10 - imiti gakondo ihura n’ubuvuzi bitewe no gufata nabi mito cyangwa iy'uburozi bukabije. Kubwibyo, harakenewe cyane guteza imbere uburyo bunoze bwo kuvura.

Kunanirwa k'umutima biterwa no guhangayika byerekana imwe mu mpamvu zambere zitera kunanirwa k'umutima ku isi yose, hamwe na patrophysiologie yayo ifitanye isano rya bugufi n'imikorere mibi ya mitochondial na fibrosis ya myocardial interstitial. Kumenya uburyo bwiza bwo kuvura nibyingenzi mugutezimbere ibisubizo byabarwayi. Kubera iyo mpamvu, abashakashatsi bakoze SS-31, igitabo cyitwa antioxydeant ya mitochondrial yibasiwe na mitochondial, kugirango bakemure ibikenerwa byo kuvura indwara ziterwa na mitochondial. Ikora cyane cyane mumbere ya mitochondrial imbere, igahindura imiterere ya mitochondial n'imikorere mugihe igabanya imbaraga za okiside, ikerekana imikorere muburyo butandukanye bw'indwara.

Ni ubuhe buryo bwo gukora bwa SS-31?

Kugenzura imikorere ya mitochondrial membrane imikorere

Imikoranire na cardiolipine: Elamipretide yambukiranya imitsi yo hanze ya mitochondrial kandi ihuza kardiolipine. Cardiolipine ni ikintu cy'ingenzi cya fosifolipide igizwe na mitochondrial y'imbere, igira uruhare runini mu kubungabunga imiterere n'imikorere ya mito-iyambere. Binyuze muri iyi mikoranire, Elamipretide itezimbere bioenergetike ya mitochondrial na morphologie. Ubu buryo bugaragara nko kongera imbaraga mu mikorere ya mitochondial mu ngirabuzimafatizo ziterwa na pluripotent, cyane cyane mu ngirabuzimafatizo zikomoka ku barwayi barwaye syndrome ya Barth ndetse n’indi ndwara y’umutima y’abana bato ^[1].

Guhindura imiterere yumubiri: Ubushakashatsi bwa Mitchell W bwerekana ko Elamipretide ikorana na lipide bilayeri, ihindura imiterere yumubiri wa mitochondrial membrane, cyane cyane imiterere ya electrostatike kuri membrane. Iyi peptide ikwirakwiza muri membrane intera yakarere hamwe nubusabane hamwe nubucucike bufitanye isano nuburyo bwo kwishyurwa hejuru. Nubwo idahagarika bilayeri ya lamellar murwego rwo hejuru, itera impinduka zuzuye muburyo bwa lipide, bityo bikagira ingaruka kumikorere ya mitochondrial membrane ^[2].

Igishushanyo 1 Ibintu bigira ingaruka kumitima yumutima no kubisabwa ^[1].

Kurinda Sisitemu Nervous

Gutezimbere Imikorere Yubwenge: Muri lipopolysaccharide (LPS) -imbeba yimbeba yatewe no kutibuka neza, kuvura Elamipretide byateje imbere cyane ubushobozi bwo kwiga no kwibuka mumazi ya Morris maze (MWM) hamwe nibizamini byo gutinya ahantu. Izi ngaruka nziza zishobora kuba zifitanye isano no kurinda imikorere ya mitochondial, kugabanya imihangayiko ya okiside, kugenga ubwonko bukomoka mu bwonko bukomoka mu bwonko (BDNF) bwerekana inzira, no kongera imiterere igoye. Ubuvuzi bwa LPS bwateje imikorere mibi ya mitochondial, guhangayikishwa na okiside, gutwika, apoptose ya neuronal, no gutakaza umugongo wa dendritic muri hippocampus yimbeba, mugihe Elamipretide yagabanije izo nkomere, byerekana ubushobozi bwo gukumira imikorere mibi ya neurocognitive (PND) ^[3].

Kubuza Apoptose ya Neuronal: Mu bushakashatsi bw’imvune y’umugongo (SCI), Elamipretide iteza imbere gukira mu guhagarika pyroptose, kongera autophagy, no kugabanya lysosomal membrane permeability (LMP). Itezimbere autophagy muguhagarika cPLA2 fosifora mugihe igabanya pyroptose na LMP. Niyo mpamvu, Elamipretide igira uruhare runini mu gusana ibikomere by’imitsi mu kugenzura imikorere myinshi ya selile, kugabanya apoptose ya neuronal, no guteza imbere imikorere y’imitsi ^[4].

Igishushanyo 2 Elamipretide (SS-31) yongereye imbaraga za okiside hamwe nigisubizo cyo gutwikwa cyatewe na LPS muri hippocampus yimbeba. ubwoko bwa ogisijeni ikora (ROS), b malondialdehyde (MDA), hamwe na c superoxide disutase (SOD) ^[3].

Ni ubuhe buryo bukoreshwa muri SS-31?

Indwara ya Neurologiya

Kuvura ihahamuka rya Optic Neuropathie: Ihahamuka rya optique neuropathie (TON) rirashobora gutera intumbero ihoraho kubera ihungabana rya orbital. Ubushakashatsi bwakoze ubushakashatsi ku ngaruka za neuroprotective ya SS-31 zifatanije n’ikibyimba cya nérosose (TNF) inhibitor etanercept kuri selile retinal ganglion (RGCs) nyuma yo gukomeretsa imitsi ya optique. Ubushakashatsi bwa Tse BC bwifashishije imbeba ya ultrasound iterwa na TON (SI-TON) bwerekanye ko inshinge za intravitreal zatewe na SS-31 zifatanije no gutera inshinge zo mu bwoko bwa etanercept na SS-31 byongereye cyane ubuzima bwa RGC ku gipimo cya 21% (p <0.01) ugereranije na saline ya fosiferi (PBS) -amaso yo kugenzura. Gutera inshinge ziterwa na etanercept na SS-31 byongereye RGC kubaho 11% (p <0.05) ugereranije no kugenzura; Gutera insimburangingo ya etanercept yonyine byongereye RGC kubaho 20% (p <0.01) ugereranije no kugenzura; Gutera inshinge za SS-31 byonyine byongereye RGC kubaho 17% ugereranije nitsinda rishinzwe kugenzura (p <0.01). Ubu bushakashatsi bwerekana ko SS-31 igira ingaruka zo gukingira RGCs mu kuvura indwara ya neuropathie ihahamuka, bityo bigatuma ubushishozi bugaragara ku barwayi ba TON ^[5].

Gutezimbere muri α-Synuclein Ifitanye isano na Neurodegenerative Indwara: Indwara ya Parkinson hamwe na synucleinopathies ifitanye isano rya bugufi bifitanye isano na membrane ihuza hamwe no gukusanya α-synuclein. Ubushakashatsi bwa Stefaniak bwemeza ko SS-31 ishobora kwimura bitewe n’imiterere y’ishyamba na N-terminal acetylated α-synuclein iva mu mitsi mito ya monolayeri itemewe, ikabuza membrane iterwa na α-synuclein, kandi igahindura imitekerereze ya fibrillar. Byongeye kandi, SS-31 igarura iyimurwa rya synuclein ivuye mu mitsi mito ya monolayeri yuzuye nabi, ikabuza guterana kwa membrane-iterwa na α-synuclein, kandi igahindura imitekerereze ya fibrillar. Byongeye kandi, SS-31 irashobora kugarura iyimurwa rya synuclein - iturutse ku mitsi mito ya unilamellar yuzuye nabi, ikabuza membrane iterwa na α-SNIP guteranya, kandi igahindura imitekerereze ya fibrillar. Byongeye kandi, SS-31 yagaruye imikorere ya mitochondrial yangiritse mu ngirabuzimafatizo ya neuroblastoma ivurwa na α-SNIP oligomers kandi ikabuza gufata selile ya oligomeri. Ibyavuye mu bushakashatsi byerekana ingaruka za SS-31 zo kurinda ibintu byinshi birinda α-synuclein igiteranyo cyatewe na mitochondrial dysfonctionnement, ikagishyira mu rwego rwo kugabanya indwara zifata ubwonko zifitanye isano na α-synuclein zitemewe no guteranya ^[6].

Indwara z'umutima

Kunoza imikorere ya Mitochondrial abarwayi bananirwa kumutima: Guhindura mitochondial mbi bizwi ko bibaho mubarwayi bananirwa kumutima (HF). Ubushakashatsi bwakoresheje uburyo bushya bwa vivo bwananiranye kandi butananirwa gutsindira ingirabuzimafatizo kuva ku bana ndetse no ku bantu bakuru bafite SS-31, bapima umwuka wa ogisijeni wa mitochondrial, ibintu bigoye (C) I na CIV, hamwe n’ibikorwa bishingiye kuri gel byo guterana kwa supercomplex. Ibyavuye muri Chatfield byerekana imikorere mibi ya mito-iyambere mu mitima yabantu. Nyuma yo kuvura SS-31, okisijeni ya mitochondrial flux, ibikorwa bya CI na CIV, hamwe nigikorwa cya CIV kijyanye no guterana kwa supercomplex byateye imbere ku buryo bugaragara, byerekana ko SS-31 yongerera imbaraga imikorere ya mitochondial mu mitima yabantu kandi ikagira uruhare mu kunanirwa k'umutima ^[7].

Umuti wa Barth Syndrome Cardiomyopathie: Indwara ya Barth ni indwara idasanzwe kandi ishobora guhitana abantu X ifitanye isano n’impfu nyinshi z’abana ndetse no gutera imbere kwa cardiomyopathie hamwe n’ubumuga bukomeye bw’umubiri. S. Itezimbere ubuzima bwa selile kandi igabanya imbaraga za okiside mukongera ingufu zingufu no guhagarika ubwoko bwa ogisijeni ikabije. Ubushakashatsi bwa Sabbah bwerekana ko SS-31 itezimbere byihuse bioenergetike ya mitochondrial na morphologie mu ngirabuzimafatizo ya pluripotent stem selile ikomoka ku barwayi barwaye syndrome ya Barth. Imibare yaturutse ku ngero nyinshi z’indwara zerekana ko SS-31 ifite amasezerano nk’ubuvuzi bushobora kuvura abarwayi bafite indwara ya Barth syndrome yumutima, bikagaragaza ingaruka zigaragara cyane ku basuzumwe indwara zifata umutima. Irashobora kugira ingaruka zirambye kumutima utera imbere mugihe gahoro gahoro gahindura uburyo bwo guhindura imikorere yibumoso bwananiwe kurwego rwisi, selile, na molekile ^[1] .

Indwara ya Musculoskeletal Indangagihe: Yerekanye ubushobozi bwo kuvura muri tendinopathie. Ubushakashatsi bwa Zhang X bwakoresheje urugero rwimbeba supraspinatus tendinopathie, igabanya imbeba 126 (ingingo 252) mumatsinda atandatu yubushakashatsi. Ibisubizo byatanzwe na Zhang X byerekana ko imbaraga zo guturika zagabanutse nyuma yingaruka ugereranije nudukoko twiza. Uku kugabanuka kwahinduwe igice nyuma yo gukuraho clamp, kuvura SS-31, cyangwa kuvura hamwe, hamwe no gukomera byerekana uburyo busa. Isesengura ry’amateka ryerekanye amanota menshi ya Bonar yahinduwe mu itsinda ry’ingaruka, mu gihe ubuvuzi bwahujwe bwahinduye igice cyahinduye imiterere ya morfologiya. Itsinda ryibasiwe ryagaragaje umubare wa mitochondrial yagabanutse kandi uhindura cristae nubucucike. Nyuma yo kuvanaho clamp hamwe na / cyangwa SS-31 kuvura, imiterere ya mitochondial nubunini byari bisanzwe, na morphologie ya cristae yarateye imbere. Ibikorwa bya Superoxide (SOD) byagabanutse nyuma yingaruka ugereranije nubugenzuzi ariko byiyongereye cyane nyuma yo kuvurwa, cyane cyane mumatsinda avura. Imvugo ya geno ya Mitochondria yagabanutse mu itsinda ry’ingaruka ariko yongeye kwiyongera nyuma yo kuvurwa. Ibi birerekana ko SS-31, nkumurinzi wa mito-iyambere, itezimbere imikorere ya mito-iyambere kandi igateza imbere gukira imitsi, hamwe ningirakamaro mugihe iyo ihujwe no gukuraho subacromial impingement. Ifite ubushobozi bwiza bwo kuvura supraspinatus tendinopathie [8].

Umwanzuro

SS-31 (Elamipretide), nka tetrapeptide yibasiwe na mitochondial, igera ku kurinda imikorere ya mito-iyambere no gusana ibikomere byinshi. Ihuza na fosifatidylserine munda yimbere ya mitochondrial imbere, igahindura imiterere ya membrane hamwe nubushobozi bwayo, ikongera ibikorwa byuruhererekane rwubuhumekero kugirango iteze imbere umusaruro wa ATP, kandi itezimbere ingufu za selile. Icyarimwe, irwanya ubwoko bukabije bwa ogisijeni (ROS) ikabije, igenga ibikorwa bya enzyme ya antioxyde, kandi ikagabanya kwangirika kwa okiside. Kubirebana no gutwika umuriro, birabuza gukora NF-κB na NLRP3 inflammasome, bigabanya gusohora ibintu. Ihindura inzira ya autophagy, irwanya apoptose, kandi ikomeza mitochondrial homeostasis ikoresheje inzira zijyanye. Ibi bikorwa bitanga ingaruka zingirakamaro mu ndwara zirimo imikorere mibi ya mitochondial sisitemu yumutima, imitsi, imitsi, na musculoskeletal.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Kathryn C. Chatfield ni umushakashatsi mu ishuri ry’ubuvuzi rya kaminuza ya Colorado, ifitanye isano n’ishami ry’abana n’ubuvuzi / Ishami ry’umutima. Yibanze ku ndwara z'umutima z'abana na biologiya ya mitochondrial, akora ubushakashatsi ku mikorere ishingiye ku mikorere y'umutima n'indwara. Yagize uruhare runini muri urwo rwego abinyujije mu bitabo by’abahanga n’ubufatanye, kandi umurimo we urashimirwa mu guteza imbere imyumvire y’imiterere yimitsi yumutima hamwe ningamba zo kuvura. Kathryn C. Chatfield yanditse murutonde rwibisobanuro [7].

Imirongo ijyanye

Sabbah HN. Elamipretide ya syndrome ya Barth syndromeomy: kwiyubaka buhoro buhoro ya gride yamashanyarazi. Isubiramo ry'umutima 2022; 27 (5): 1911-1923.DOI: 10.1007 / s10741-021-10177-8.

[2] Mitchell W, Ng EA, Tamucci JD, n'abandi. Uburyo bwa molekuline bwibikorwa bya Mitochondrial Therapeutic SS-31 (Elamipretide): Imikoranire ya Membrane ningaruka kuri Electrostatics yo hejuru. Biorxiv 2019. Https://api.semanticscholar.org/CorpusID:202016574.

[3] Zhao W, Xu Z, Cao J, n'abandi. Elamipretide (SS-31) itezimbere imikorere mibi ya mitochondrial, synaptic hamwe nubumuga bwo kwibuka buterwa na lipopolysaccharide mumbeba. Ikinyamakuru cya Neuroinflammation 2019; 16(1): 230.DOI: 10.1186 / s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, n'abandi. Elamipretide igabanya pyroptose mumyanya yumugongo yakomeretse cyane muguhagarika cPLA2 iterwa na lysosomal membrane permeabilisation. Ikinyamakuru cya Neuroinflammation 2023; 20(1): 6.DOI: 10.1186 / s12974-023-02690-4.

[5] Tse BC, Dvoriantchikova G, Tao W, n'abandi. Mitochondrial yibasiwe nubuvuzi hamwe na elamipretide (MTP-131) nkumugereka wibibyimba bya nérosose bibuza kwandura indwara ya neuropathie ihahamuka mugihe gikabije. Ubushakashatsi bw'amaso y'ubushakashatsi 2020; 199: 108178.DOI: 10.1016 / j.exer.2020.108178.

] Biorxiv 2024. Https://api.semanticscholar.org/CorpusID:271162443.

[7] Chatfield KC, Sparagna GC, Chau S, n'abandi. Elamipretide Itezimbere Imikorere ya Mitochondrial mumutima wumuntu wananiwe. Jacc-Shingiro kubumenyi bwubuhinduzi 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 SA. SS-31 nkumurinzi wa Mitochondrial mukuvura Tendinopathie: Isuzuma muri Murine Supraspinatus Tendinopathie Model. Ikinyamakuru cyamagufwa hamwe no kubaga hamwe-Umubumbe wa Amerika 2022; 104 (21): 1886-1894.DOI: 10.2106 / JBJS.21.01449.

INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.  

Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.