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1kits （10Ibikoresho）
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▎ Imiterere ya SS-31
Inkomoko: PubChem |
Urukurikirane: RXKF Inzira ya molekulari: C 32H 49N 9O.5 Uburemere bwa molekuline: 639.8g / mol Numero ya CAS: 736992-21-5 PubChem CID: 11764719 Synonyme: Elamipretide |
SS SS-31 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na SS-31?
SS-31 ni amazi ashonga, aromatic cationic, tetrapeptide yibasiwe na mitochondria (Sabbah HN, 2022). Imiterere yihariye ya chimique ituma yinjira byoroshye kandi igahinduka mugihe gito imbere ya mitochondrial imbere. By'umwihariko, irashobora guhuza na cardiolipine, igice kinini cyimiterere yimbere ya mito-iyambere, bityo ikagira ingaruka zo kunoza imikorere ya mito-iyambere.
Iyi miti yihariye itanga umusingi wo kuyikoresha mu kuvura indwara zitandukanye. Indwara nyinshi zifitanye isano no kudakora neza kwa mitochondrial, nka syndrome ya Barth, kunanirwa k'umutima, indwara zifata ubwonko, n'ibindi. Iyo imikorere ya mitochondial ibangamiwe, irashobora gukurura ibibazo nkingufu zidahagije zingirabuzimafatizo, kongera imbaraga za okiside, hamwe na neuroinflammation, nayo igatera indwara zitandukanye.
Ubushakashatsi n’iterambere rya SS-31 bigamije kwibasira izo ndwara ziterwa na mitochondial, kugabanya ibimenyetso by’indwara mu kunoza imikorere ya mito-iyonona no kuzamura imibereho y’abarwayi n’imibereho yabo. Hamwe nubushakashatsi bwimbitse bwibanze kuri biologiya ya mitochondrial, abantu bamenye buhoro buhoro akamaro ka mitochondriya muguhinduka no gutera indwara.
Abashakashatsi basanze imikorere mibi ya mitochondrial ifitanye isano rya hafi na patrophysiologique yindwara zitandukanye. Kurugero, mu ndwara zifata ubwonko, hariho ibibazo nka imikorere mibi ya mitochondrial neuronal, imikorere ya neuroinflammation idakira, kwegeranya poroteyine z'ubumara, na apoptose ya neuronal [1] . Mbere yo kwinjira mu bushakashatsi ku mavuriro, SS-31 yakorewe ubushakashatsi bwimbitse. Ubu bushakashatsi bwarimo ubushakashatsi bwakozwe ku ngero z'utugari no ku nyamaswa kugira ngo hamenyekane umutekano, imikorere, n'imiti ya farumasi. Kurugero, mubushakashatsi bwa syndrome ya Barth, SS-31 yerekanye ubushobozi bwo kuzamura byihuse bioenergetike ya mitochondrial na morphologie muburyo bwimikorere ya selile pluripotent [2].
Mu bushakashatsi bwakozwe ku ndwara zifata ubwonko, SS-31 yerekanye ingaruka za neuroprotective mu ngero nyinshi z’inyamaswa, harimo kongera imbaraga zo guhumeka mitochondial, kubuza neuroinflammation, no kwirinda kwirundanya kwa poroteyine zifite ubumara [1] . SS-31 yamaze kugira uruhare mubushakashatsi butandukanye buvura indwara zitandukanye.
Mu kuvura kunanirwa k'umutima, igeragezwa ryateganijwe, rigenzurwa na platbo ryerekanye ko kwinjiza kimwe kwa SS-31 bifite umutekano kandi byihanganirwa, kandi urugero rwinshi rwa SS-31 rushobora kuzamura ingano y’ibumoso, rushyigikira uruhare rwarwo mu kuvura indwara z’umutima [3].
Nubuhe buryo bwihariye bwibikorwa bya SS-31 muburyo butandukanye bwindwara?
1. Uburyo bwibikorwa muburyo bwo guterwa no kuva amaraso hamwe na ballon ya aortic
Mu cyitegererezo cy’imvune ya ischemia-reperfusion (IRI) iterwa no guhungabana kwa hemorhagie hamwe na ballon ya aortic (REBOA), kwangirika kwa mitochondial bigira uruhare runini. SS-31 irashobora kugabanya ibyifuzo byamazi ya kristalloide kandi ikarinda impyiko numutima. By'umwihariko, irashobora kugabanya ubukana bwa serumu creatinine, troponine, na interleukin-6, ariko nta ngaruka igira ku kwibumbira kwa plasma ya nyuma. SS-31 irashobora kugabanya IRI ikingira mitochondriya, igafungura inzira nshya zo kuvura abarwayi barwaye IRI nyuma yo kuva amaraso [4].
2. Uburyo bwibikorwa muri syndrome ya Barth
Indwara ya Barth ni indwara idasanzwe X ifitanye isano na cardiomyopathie, intege nke z'imitsi ya skeletale, kudindira gukura, na neutropenia cyclic. S. Itera imbere ubuzima bw'utugingo ngengabuzima iteza imbere ingufu kandi ikabuza gukora cyane ubwoko bwa ogisijeni ikora, bityo bikagabanya imbaraga za okiside. Muri selile pluripotent stem selile ya Barth syndrome nizindi ndwara zifitanye isano na genetique zirangwa na cardiomyopathie yo mu bwana, SS-31 irashobora guteza imbere byihuse bioenergetike ya mitochondrial na morphologie. Ibyavuye mu bushakashatsi bwinshi bishyigikira ikoreshwa rya SS-31 nk'ubuvuzi bushobora kuvura abarwayi barwaye syndrome ya Barth, cyane cyane mu gihe basuzumye indwara z'umutima ..
3. Uburyo bwibikorwa muri autosomal yiganje yindwara yimpyiko (ADPKD)
Inda ifatwa nk'iyongera umuvuduko wa cysts mu ndwara zifata impyiko za autosomal yiganje (ADPKD). Nyamara, tolvaptan, imiti yonyine yemejwe na FDA kubantu bakuze ADPKD, ntabwo isabwa abarwayi ba ADPKD batwite kubera ingaruka zishobora kwangiza uruhinja. SS-31 ni tetrapeptide irinda mitochondriya yabonetse kugira ngo iteze imbere iterambere ry’indwara zimpyiko ku mbeba za Pkd1RC / RC zitwite, mu gihe zigabanya fosifori ya ERK1 / 2 no kunoza imitekerereze ya mito-iyambere. Byongeye kandi, SS-31 irashobora kwambuka insina n'amata yonsa, igateza imbere impyiko zimpyiko zimpyiko zidafite ingaruka mbi za teratogene cyangwa mbi. Ubu bushakashatsi bwibanze bushyigikira ibizamini bya kliniki ya SS-31 [5].
4. Uburyo bwibikorwa mukunanirwa k'umutima
Kunanirwa k'umutima (HF), impinduka mbi muri mitochondriya izwiho kubaho. SS-31 igira ingaruka nziza kumikorere ya mitochondrial na supercomplex imikorere yumutima wumuntu. Irashobora kongera cyane umwuka wa ogisijeni, ibikorwa bya I hamwe n’ibikorwa bya IV bigoye, hamwe n’ibikorwa bya IV bigoye bifitanye isano na supercomplexes mu mitima ya mitochondriya y’umutima yacitse intege, bikanoza cyane imikorere y’imikorere ya mito-iyambere [6].
Ku bana bafite uburwayi bw'umutima umwe (SV CHD), ibimenyetso byerekana ko umuntu ahindura umutima byerekana ko hari imikorere mibi ya mito-iyambere. SS-31 ni pentapeptide yibasira kardiolipine ishobora kunoza imikoranire ya supercomplexes ya mitochondrial (complexe I, III, IV). Mu mitima y'abana barwaye SV CHD, SS-31 irashobora kunoza ibikorwa bigoye I hamwe no guhumeka ntarengwa (MR), byerekana ko ahanini bigira ingaruka nziza mugutezimbere supercomplexes ya mitochondial [7].
5. Uburyo bwibikorwa muri diabete ya nepropatique
Muburyo bwimbeba ya db / db ya diyabete yo mu bwoko bwa 2, nepropatique diabete (DKD) ifitanye isano no kugabanuka kwurwego rwimpyiko na cardiac superoxide. Imiti ikingira mitochondria SS-31 (izwi kandi nka MTP-131, SS-31, cyangwa Bendavia) irashobora kubuza cyane kwiyongera kwa proteinuria, inkari H₂O₂, hamwe na glomerular mesangial matrix kwirundanya mu mbeba za db / db, kandi bikarinda rwose urugero rw’umusemburo wa superoxide muri izo mbeba. SS-31 irashobora kandi kugabanya lysocardiolipine yimpyiko zose hamwe ningenzi nyamukuru ya lysocardiolipin mu mbeba za db / db, kandi ikarinda imvugo ya lysocardiolipin acyltransferase 1.Ibisubizo byerekana ko muburyo bwa diyabete yo mu bwoko bwa 2, DKD ifitanye isano no kugabanuka kurwego rwa superoxide yumutima na SSK 31. kuvugurura [8].
Igishushanyo cya hypothesize cyerekana muri make ingaruka za neuroprotective ya elamipretide kuri neuron ya mitochondria-kugenzura ubuziranenge.
Inkomoko: Byatangajwe [1]
Ni ubuhe buryo bujyanye na SS-31?
Indwara ya Cardiomyopathie muri syndrome ya Barth: Indwara ya Barth ni indwara idasanzwe kandi ishobora guhitana ubuzima bwa X ifitanye isano na cardiomyopathie, intege nke z'imitsi ya skeletale, kudindira gukura, na neutropenia. Abarwayi bafite ibyago byinshi byo gupfa bakiri bato kandi bakunze guhura n'indwara z'umutima hamwe no gucika intege gukabije k'umubiri. SS-31 irerekana ibibazo n'amahirwe yo kuvura indwara z'umutima ku barwayi barwaye syndrome ya Barth. Ibisubizo byubushakashatsi bwinshi bishyigikira ikoreshwa ryabyo nkubuvuzi bushobora kuvura abarwayi ba syndrome ya Barth, cyane cyane iyo indwara ya cardiomyopathie isuzumwe. Irashobora kugira ingaruka zirambye ku iterambere rya cardiomyopathie kandi buhoro buhoro kandi bigahindura uburyo bwo guhindura imikorere y’ibumoso bwananiranye ku rwego rwisi, selile, na molekile [2].
Indwara imwe yumutima ivuka:
Indwara z'umutima zavukanye nizo nenge zikunze kuvuka, kandi indwara zikomeye z'umutima zivuka ni kimwe mu bintu nyamukuru byerekana kwimura umutima, hakaba hari uburyo buke bwo kuvura ubu. Byagaragaye ko hari imikorere mibi ya mitochondial mu mitima y’abana bafite indwara imwe y’umutima ivuka, kandi peptide SS-31 yibasiwe na mitochondria irashobora kunoza imikorere ya mitochondial yumutima. Ubushakashatsi burambuye ku bushobozi bwibi biyobyabwenge bwo kunoza imikorere ya myocardial no gutinza iterambere rya transplantation birakenewe [7].
Leber's hereditary optic neuropathie:
Ubushakashatsi bwerekanye umutekano, ubworoherane, n’ingaruka zishobora gukoreshwa mu gukoresha SS-31 mu kuvura abarwayi bafite indwara ya neberopathie ya Leber's hereditaire. Ibisubizo byerekanaga ko SS-31 yihanganiye neza, ariko itageze kumurongo wambere wibanze. Nyamara, isuzuma ryimikorere yibikorwa mugihe cyo gufungura-label mugihe cyo kwagura no gusesengura nyuma ya hoc byagaragaje gutera inkunga gutera imbere hagati yo gutandukana hagati yumurima wo hagati, bisaba ko hakorwa ubushakashatsi [9].
Ihahamuka rya optique neuropathie:
Byagaragaye ko SS-31 (MTP-131), mitochondriya yibasiwe na molekile ntoya ya tetrapeptide, iyo ikoreshejwe ifatanije n’ikibyimba cyitwa nekrosis factor inhibitor etanercept, ishobora gukora nka neuroprotectant ya selile retinal ganglion nyuma yo guhahamuka kwa nervice optique mu mbeba. Etanercept ya Subcutaneous cyangwa MTP-131 yonyine kandi guhuza kwabo byose bishobora kongera igipimo cyo kubaho kwingirabuzimafatizo ya retinal ganglion, ariko nta ngaruka zo guhuza imbaraga zagaragaye igihe zakoreshwaga hamwe [10].
Gukomeretsa uruti rwumugongo: SS-31 (SS-31) nigitabo gishya cyitwa aromatic cationic peptide gishobora kurenga kubusa inzitizi yubwonko bwamaraso. Ubushakashatsi bwerekanye ko SS-31 iteza imbere gukira nyuma yo gukomeretsa uruti rwumugongo hirindwa kwangirika kwa autophagic cPLA2, kurinda ubwiyongere bwa lysosomal membrane, no kubuza pyroptose, kandi ifite agaciro k’ubuvuzi [11].
Neuroinflammation no kutamenya ubwenge:
Imbeba zishaje, lipopolysaccharide irashobora gutera uburibwe bwa sisitemu na neuroinflammation, kandi SS-31 irashobora gukoreshwa mukuvura. Ubushakashatsi bwerekanye ko kubuza hippocampal neuroinflammation bidashobora kugabanya gusa ingaruka ziterwa na hippocampus gusa ahubwo binateza imbere imikorere yubwonko mukarere kajyanye na hippocampus. Ubuvuzi bwambere bwo kurwanya inflammatory hamwe na SS-31 bugira ingaruka zirambye mukugabanya ingaruka za lipopolysaccharide iterwa na neuroinflammation [12].
Indwara yimpyiko yiganjemo Autosomal:
Inda ifatwa nk'iyongera umuvuduko wa cysts mu ndwara zifata impyiko za autosomal. Byagaragaye ko tetrapeptide ya mitochondriya irinda SS-31 ishobora guteza imbere indwara z’impyiko ku mbeba za Pkd1 ^ {RC / RC}, mu gihe zigabanya fosifori ya ERK1 / 2 no kunoza imitekerereze ya mito-iyambere. SS-31 irashobora kwambuka insina n'amata yonsa, igatera indwara zikomeye zimpyiko zimpyiko zidafite ingaruka za teratogene cyangwa mbi ..
Indwara zifata ubwonko:
SS-31 ni mitochondriya yibasiwe na molekile ntoya ya tetrapeptide yerekanye ingaruka zo kuvura n'umutekano mu ndwara zitandukanye ziterwa na mitochondial. Mu ndwara zifata ubwonko, SS-31 irashobora kongera ubuhumekero bwa mitochondial, igakora mikorobe ya mitochondrial biogenezi ikoresheje mitochondrial biogenesis igenga ibintu hamwe na translocator, kongera imbaraga za mitochondrial fonctionnement, kubuza mitochondrial fonctionnement, kongera mitofagy, kugabanya imitekerereze ya neuronal, no kwanduza inzira za poroteyine, Kubwibyo, SS-31 irashobora kubuza iterambere ryindwara zifata ubwonko mu kongera imbaraga zo guhumeka mitochondrial, biogenezi, fusion, hamwe ninzira yo kubaho ya neuronal, ndetse no kubuza kwandura mitochondrial, stress oxydeide, neuroinflammation, kwirundanya kwa poroteyine z'ubumara, hamwe na apoptose ya neuronal [1].
Sarcopenia: Byagaragaye ko ibyumweru 8 byo kuvura hamwe na SS-31 bishobora guhindura igice kijyanye n’imyaka ihindagurika ry’imyaka muri poroteyine fosifora mu mitsi ya skeletale y’imbeba z’abagore bageze mu zabukuru, ibyo bikaba bijyana no kunoza imikorere y’imitsi ya skeletale no kugarura impinduka muri poroteyine S-glutathionylation [13].
Nkumuti wibasiwe na mitochondriya, SS-31 itanga ingamba nshya zo kuvura indwara ziterwa na mitochondial. Mu kurinda imiterere n'imikorere ya mitochondriya, yerekanye agaciro kivuriro mu ndwara nka syndrome ya LHON na Barth, cyane cyane yerekana akamaro gakomeye muri neuropathie acute optique. Ifite ingaruka zo kuvura indwara zitandukanye zijyanye no kudakora neza kwa mitochondrial, nko kunanirwa k'umutima n'indwara zifata ubwonko, kandi birashobora kugabanya ibimenyetso no gutinza iterambere ryindwara.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Daneshgar N ni intiti ikomeye mumuryango w’amasomo, kandi umwuga we w’amasomo ufitanye isano rya hafi na kaminuza ya Iowa na kaminuza ya Leta ya Oregon. Ibikorwa bye by'ubushakashatsi ni byinshi kandi byimbitse, bikubiyemo amasomo menshi nka geriatrics na gerontologiya, sisitemu y'umutima n'imitsi, umutima, ibinyabuzima na molekuline biologiya, ibinyabuzima by'ingirabuzimafatizo, na oncologiya. Mu rwego rwa geriatrics na gerontologiya, Daneshgar N yiyemeje gushakisha uburyo bw’ibinyabuzima bwo gusaza no gufata ingamba zifatika ku ndwara ziterwa no gusaza, yizera ko ubuzima bw’abasaza buzamura ubuzima ndetse n’ubuzima bw’abasaza binyuze mu bushakashatsi.
Mu rwego rwa sisitemu yumutima nimiyoboro yumutima, akora ubushakashatsi bwimbitse kubyerekeye indwara ziterwa na virusi, uburyo bwo gusuzuma, hamwe ningamba zo kuvura indwara zifata umutima, agira uruhare mu gukumira no kuvura indwara zifata umutima. Mu rwego rwibinyabuzima na biyolojiya y’ibinyabuzima, yibanze ku miterere, imikorere, n’imikoranire ya biomolecules, agaragaza amayobera y’ibikorwa byubuzima ku rwego rwa molekile no gutanga ishingiro ry’imyumvire yo gusobanukirwa no kuvura indwara. Mu rwego rwa biologiya selile, Daneshgar N yibanze ku miterere, imikorere, n amategeko yibikorwa byubuzima bwingirabuzimafatizo, yiga inzira zingenzi nko guhererekanya ibimenyetso byingirabuzimafatizo no kugenzura ingirabuzimafatizo, bitanga ibimenyetso byingenzi byiga ku ngirabuzimafatizo z’indwara. Mu rwego rwa oncology, yiyemeje gukora ubushakashatsi ku buryo bwo kubaho no guteza imbere ibibyimba, ndetse no gusuzuma no kuvura ibibyimba, gushakisha ibimenyetso byerekana hakiri kare ndetse n’intego nshya zo kuvura ibibyimba, bizana ibyiringiro bishya ku barwayi b’ibibyimba. Daneshgar N yanditse murutonde rwibisobanuro [5].
