Na Cocer Peptides 
hashize iminsi 30
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.
Incamake
SS-31, izwi kandi nka Elamipretide, ni peptide ya aromatic cationic cationic. SS-31 irashobora kurenga kubuntu inzitizi yubwonko bwamaraso, umutungo utuma bikwiranye no kuvura indwara zifata ubwonko. Inzitizi y'amaraso n'ubwonko ikora nk'inzitizi ikomeye yo gukingira sisitemu yo hagati, hamwe n'imiti myinshi irwana nayo. Nyamara, SS-31 yatsinze iyi mbogamizi, igera aho yangiritse kandi ikanatanga ibyiringiro byo gusana ibyangiritse. Ni mubyiciro bya peptide ntoya-ifite molekile ntoya, ifite uburemere buke bwa molekile, itanga imbaraga nziza hamwe na bioavailable mumubiri. Cation yatwawe na SS-31 ituma ishobora gukorana nibice bitarimo ibice byibinyabuzima, cyane cyane imbere yimbere ya fosifolipide yimbere ya mitochondria. Ihuza ryihariye ryemerera SS-31 kwirundanya muri mitochondriya, bityo ikagira ingaruka zayo mumikorere ya mito-iyambere.
Igicapo 1 Uburyo bwibikorwa bya SS-31 kurwanya indwara zimpyiko.
Uburyo bwibikorwa
Amabwiriza yimikorere ya Mitochondrial
Mitochondria, nk'imbaraga z'ingirabuzimafatizo, igira uruhare runini mu mibereho ya selile no guhindagurika. S. Inzira y'ubuhumekero ya mitochondrial ni inzira ikomeye yo kubyara ingufu za selile (ATP). SS-31 itezimbere imikorere ya poroteyine zijyanye no guhumeka, kuzamura imikorere ya transport ya elegitoronike, bityo bigateza imbere synthesis ya ATP no guha selile imbaraga zihagije zo gukomeza ibikorwa bisanzwe byumubiri nko kugabana selile, gutandukanya, no gutwara ibintu.
SS-31 ikora mitochondrial biogenezes muri neuron, iteza imbere mitochondriya nshya. Iyo selile zihuye n’ibyangiritse cyangwa imihangayiko, kubyara mitochondriya nshya bifasha kuzuza mitochondriya yangiritse cyangwa idakora neza, ikomeza ubuzima bwabaturage ba mitochondial muri selire. Itezimbere kandi mitochondrial autophagy, uburyo bwa selile yo gukuraho mitochondriya yangiritse. Niba mitochondriya yangiritse idahanaguwe vuba, irekura ubwoko bwinshi bwa ogisijeni ikora (ROS), bikangiza ingirabuzimafatizo. SS-31 igabanya neza umusaruro wa ROS mukongera mitochondrial autophagy, bityo ikarinda selile kwangirika kwa okiside.
Kubuza ibisubizo byumuriro
Mubikorwa byinshi byangiza selile, ibisubizo byumuriro akenshi biherekeza ibyangiritse. Cytoplasmic phospholipase A2 (cPLA2), nkumuhuza wibanze wa neuroinflammation, isenya fosifolipide ya membrane kuri sn-2 yumwanya wa lysosomes mubihe byindwara ya pathologiya, itanga lysophospholipide na ω3 polyunsaturated fatty acide, biganisha kuri lysosomal membrane permeabilisation (LMP). SS-31 irashobora kugabanya urwego rwo kwerekana imiterere ya fosifora ya cytoplasmeque fosifolipase A2 (p-cPLA2), ikabuza fosifora ya cPLA2, bityo bikagabanya umusaruro w’abunzi batera umuriro kandi bikagabanya ibyangijwe n’ibisubizo biterwa na selile.
Mu bushakashatsi bwakozwe ku mvune ya sepsis iterwa na myocardial, SS-31 yasanze ibuza gukora NF-κB na NLRP3, bityo igatera ibisubizo bya myocardial inflammatory. NF-κB ni urufunguzo rwingenzi rwerekana inzira yerekana ibimenyetso, mugihe NLRP3 nigice cyingenzi cyumuriro. Gukora kwabo biganisha kurekura umubare munini wibintu bitera umuriro, nka IL-6, IL-1β, na TNF-α. Muguhagarika ibikorwa byibi bintu bibiri byingenzi, SS-31 igabanya imvugo yerekana ibintu bitera umuriro, igabanya kwangirika kwingirangingo za myocardial, kandi igakomeza imikorere yabo isanzwe.
Guteza imbere autophagy no kubuza pyroptose
Autophagy nuburyo bwingenzi bwo kwikingira mu ngirabuzimafatizo zangiza ingirangingo zangiritse, poroteyine zitabitswe neza, n’ibindi bintu byangiza. Mu bushakashatsi bw’imvune y’umugongo, byagaragaye ko SS-31 yongerera urwego rwa poroteyine zijyanye na autofagy nka Beclin-1, VPS34, na LC3, bigabanya urwego rwa poroteyine ziterwa na autofagy nka p62, ariko ntirugire ingaruka ku rwego rwa poroteyine ziterwa na lysosomal nka ATP6V1B2 na LAMP1. Ibi byerekana ko SS-31 ishobora kugira uruhare mu mikorere ya autophagosomes nyuma yo gukomeretsa umugongo, nka p62, bitagize ingaruka ku rwego rwa poroteyine ziterwa na lysosomal biogenezi, nka ATP6V1B2 na LAMP1. Ibi byerekana ko SS-31 ishobora kugira uruhare mu mikorere ya autophagosomes nyuma yo gukomeretsa umugongo, igatera imbere mu buryo busanzwe bw’inzira ya autofagy, ifasha ingirabuzimafatizo mu gukuraho ibice byangiritse, no kugarura umutekano w’ibidukikije.
Pyroptose ni progaramu ya inflammatory niyose itera kwangirika gukabije kwindwara zitandukanye. SS-31 igabanya urwego rwa poroteyine zijyanye na pyroptose, nka ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, na IL-18, bityo bikabuza kubaho pyroptose. Hariho imikoranire igoye hagati ya autophagy na pyroptose; kuzamura autophagy irashobora kubuza pyroptose. SS-31 igenga iyi ntera, igabanya neza impfu ziterwa na pyroptose no guteza imbere gusana no kubaho.
Porogaramu
Indwara zifata ubwonko
Gukomeretsa uruti rwumugongo nuburyo bukomeye butuma umuntu atakaza imikorere ihoraho ndetse nubumuga bwa moteri. Bitewe n'inzitizi y'amaraso n'ubwonko, imiti isanzwe irwana no kugera aho yakomeretse. SS-31, hamwe nubushobozi bwayo bwo kurenga inzitizi yubwonko bwamaraso, yerekana ubushobozi butangaje mukuvura ibikomere byumugongo. Iyo bikozwe hakoreshejwe inshinge za intraperitoneal ku mbeba zifite ibikomere byumugongo, isuzuma ryimyitwarire ukoresheje igipimo cyimbeba ya BMS, isesengura ryogukora, hamwe nipimisha ryindege ryerekanye ko biteza imbere gukira nyuma yimvune. Amateka, akoresheje HE, Masson, MAP2, na SYN yanduye, hemejwe ko SS-31 igabanya ubuso bw’umugongo w’umugongo, yongera umubare wa dendrite na synaps, kandi igateza imbere imikorere n’imikorere ya neuron yumugongo.
Mu bushakashatsi bwakozwe ku ndwara zimwe na zimwe zifata ubwonko, nk'indwara ya Parkinson n'indwara ya Alzheimer, SS-31 nayo yerekanye agaciro ko kuvura. Izi ndwara zikunze guherekezwa no guhagarika umutima biterwa no kwangirika kwa neuronal, ibisubizo byumuriro, hamwe no gukora nabi kwa mitochondrial. S.
Indwara z'umutima
Imikorere mibi yumutima nibisanzwe kandi byangiza ubuzima bwa sepsis. SS-31 yerekana ingaruka zo gukingira imvune ya myocardial muri sepsis. Mu bushakashatsi bwa vivo, imbeba zo mu itsinda rya SS-31 zagaragaje ko zateje imbere cyane imiterere ya myocardial tissue organisation hamwe no gucana umuriro ugereranije nitsinda rya sepsis, no kugabanuka gukabije kwa selile apoptotique. S. Ibi byerekana ko SS-31 ishobora guhinduka imiti ishobora kuvura umutima wa sepsis iterwa na cardiomyopathie.
Mu zindi ndwara zifata umutima, nk'imvune ya myocardial ischemia-reperfusion, SS-31 nayo ishobora kugira uruhare runini. Inzira ya myocardial ischemia-reperfusion iganisha ku musaruro mwinshi wa ROS, bigatera ibisubizo byumuriro hamwe na apoptose selile.
Umwanzuro
SS-31 irashobora kwinjira mu nzitizi y'amaraso n'ubwonko, igatera mitochondriya kugira ngo isane ibyangiritse, kandi ifite uburyo bushobora gukoreshwa mu ndwara zifata ubwonko, indwara z'umutima n'imitsi, gusana imitsi ya skeletale, no gukomeretsa kwa diyabete y'amaraso. Mu kwibasira mitochondriya nkintego yibanze, itanga inyigisho nshya yo kuvura.
Inkomoko
[1] Zhu Y, Luo M, Bai X, n'abandi. SS-31, Peptide yibasira Mitochondria, Ikiza Indwara Zimpyiko [J]. Ubuvuzi bwa Oxidative no kuramba kwa selile, 2022,2022: 1295509.DOI: 10.1155 / 2022/1295509.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
