By Cocer Peptides 
kwanaki 30 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Dubawa
SS-31, wanda kuma aka sani da Elampretide, wani labari ne na peptide na cationic. SS-31 na iya ketare shingen jini-kwakwalwa cikin yardar kaina, dukiyar da ta sa ta dace da maganin cututtukan ƙwayoyin cuta. Shamakin-kwakwalwa na jini yana aiki a matsayin babban shingen kariya ga tsarin jijiya ta tsakiya, tare da yawancin magunguna suna gwagwarmayar ketare ta. Duk da haka, SS-31 ya shawo kan wannan iyakancewa, kai tsaye ya isa wurin lalacewa na jijiyoyi kuma yana ba da bege don gyara lalacewar kwayoyin halitta. Yana cikin nau'in peptides na ƙananan ƙwayoyin cuta, tare da ƙananan nauyin kwayoyin halitta, wanda ke ba da shi tare da kyakkyawar motsi da bioavailability a cikin jiki. Cations ɗin da SS-31 ke ɗauka yana ba shi damar yin hulɗa tare da abubuwan da ba su da caji na ƙwayoyin halitta, musamman ma mummunan cajin membrane phospholipids na mitochondria. Wannan ƙayyadaddun ɗaurin yana ba SS-31 damar tarawa a cikin mitochondria, don haka yana aiwatar da tasirin sa akan aikin mitochondrial.
Hoto 1 Hanyar aikin SS-31 akan cutar koda.
Tsarin Aiki
Tsarin Ayyukan Mitochondrial
Mitochondria, a matsayin gidan makamashi na tantanin halitta, yana taka muhimmiyar rawa a cikin rayuwar salula da kuma metabolism. SS-31, tare da tsarinsa na cationic, na iya tarawa sosai a cikin phospholipids na ciki na mitochondria da ba a caji mara kyau, ta haka yana haɓaka numfashin mitochondrial. Sarkar numfashi na mitochondrial hanya ce mai mahimmanci don samar da makamashin salula (ATP). SS-31 yana haɓaka aikin sunadaran da ke da alaƙa a cikin sarkar numfashi, haɓaka haɓakar jigilar lantarki, ta haka inganta haɓakawar ATP da samar da sel tare da isasshen kuzari don kula da ayyukan ilimin lissafi na yau da kullun kamar rarraba tantanin halitta, rarrabuwa, da jigilar kayayyaki.
SS-31 yana kunna mitochondrial biogenesis a cikin neurons, yana haɓaka haɓakar sabbin mitochondria. Lokacin da sel suka fuskanci lalacewa ko damuwa, haɓakar sabon mitochondria yana taimakawa sake cika mitochondria mai lalacewa ko rashin aiki, yana kiyaye lafiyar yawan mitochondrial a cikin tantanin halitta. Hakanan yana haɓaka autophagy mitochondrial, tsarin salula don share ɓarna mitochondria. Idan ba a kawar da mitochondria da suka lalace da sauri ba, suna sakin nau'ikan iskar oxygen mai yawa (ROS), suna kara lalata sel. SS-31 yadda ya kamata rage ROS samar da inganta mitochondrial autophagy, game da shi kare sel daga oxidative danniya lalacewa.
Hana martani mai kumburi
A yawancin hanyoyin lalacewa ta salula, martanin kumburi sau da yawa yana tare da lalacewa. Cytoplasmic phospholipase A2 (cPLA2), a matsayin mai shiga tsakani na farko na neuroinflammation, ya rushe membrane phospholipids a sn-2 matsayi na lysosomes a karkashin yanayin pathological, samar da lysophospholipids da ω3 polyunsaturated m acid, haifar da lysosomal m acid. SS-31 na iya rage girman matakin magana na phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), ya hana phosphorylation na cPLA2, ta haka ne ya rage samar da masu shiga tsakani da kuma rage lalacewar lalacewa ta hanyar mayar da martani ga sel.
A cikin binciken da aka yi game da raunin ciwon zuciya na sepsis, an gano SS-31 don hana kunnawa na NF-κB da NLRP3, don haka inganta amsawar ƙwayar cuta ta myocardial. NF-κB shine maɓalli mai mahimmanci na hanyoyin siginar kumburi, yayin da NLRP3 shine muhimmin sashi na mai kumburi. Kunnawar su yana haifar da sakin babban adadin abubuwa masu kumburi, irin su IL-6, IL-1β, da TNF-α. Ta hanyar hana kunna waɗannan mahimman abubuwa guda biyu, SS-31 yana rage matakan maganganu na abubuwan da ke haifar da kumburi, yana rage lalacewar ƙwayoyin cuta na ƙwayoyin cuta, kuma yana kula da aikin su na yau da kullum.
Inganta autophagy da hana pyroptosis
Autophagy muhimmin tsari ne na kariyar kai a cikin sel wanda ke share gabobin da suka lalace, sunadaran da ba su da tushe, da sauran abubuwa masu cutarwa. A cikin nazarin raunin kashin baya, an gano cewa SS-31 yana haɓaka matakan sunadaran da ke da alaƙa da autophagy kamar Beclin-1, VPS34, da LC3, yana rage matakan furotin substrate na autophagy kamar p62, amma baya shafar matakan sunadarai masu alaƙa da lysosomal biogenesis kamar ATP6V1B2 da LAMP1. Wannan yana nuna cewa SS-31 na iya rinjayar samuwar autophagosomes bayan rauni na kashin baya, irin su p62, ba tare da rinjayar matakan sunadarai masu alaka da lysosomal biogenesis ba, kamar ATP6V1B2 da LAMP1. Wannan yana nuna cewa SS-31 na iya rinjayar samuwar autophagosomes bayan raunin kashin baya, inganta ci gaba na al'ada na hanyar autophagy, taimakawa kwayoyin halitta wajen kawar da abubuwan da suka lalace, da kuma mayar da kwanciyar hankali na yanayin ciki.
Pyroptosis wani kumburi ne wanda aka tsara shi necrosis wanda ke haifar da lalacewar salula mai yawa a cikin cututtuka daban-daban. SS-31 yana rage matakan sunadaran da ke da alaka da pyroptosis, irin su ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, da IL-18, don haka ya hana abin da ya faru na pyroptosis. Akwai rikitarwa mai rikitarwa tsakanin autophagy da pyroptosis; inganta autophagy zai iya hana pyroptosis. SS-31 yana daidaita wannan ma'auni, yadda ya kamata ya rage mutuwar kwayar halitta ta hanyar pyroptosis da inganta gyaran salula da rayuwa.
Aikace-aikace
Cututtukan Jijiya
Raunin kashin baya shine yanayin nakasa mai tsanani wanda ke haifar da asarar aiki na dindindin da nakasar mota. Saboda kasancewar shingen kwakwalwar jini, magungunan na yau da kullun suna gwagwarmaya don isa wurin da aka ji rauni. SS-31, tare da ikonsa na ƙetare shingen kwakwalwar jini, yana nuna yuwuwar yuwuwar magance raunin kashin baya. Lokacin da aka gudanar ta hanyar allurar intraperitoneal zuwa mice tare da rauni na kashin baya, kimanta halayen halayen ta amfani da ma'aunin linzamin kwamfuta na BMS, nazarin gait, da gwajin jirgin sama mai karkata ya nuna cewa yana haɓaka aikin dawowa bayan rauni. Ta hanyar tarihi, ta amfani da HE, Masson, MAP2, da SYN tabo, an ƙaddara cewa SS-31 yana rage yanki na glial scarring na kashin baya, yana ƙara yawan dendrites da synapses, kuma yana inganta tsarin aiki da gyaran gyare-gyare na ƙananan ƙwayoyin cuta.
A cikin nazarin wasu cututtukan neurodegenerative, irin su cutar Parkinson da cutar Alzheimer, SS-31 kuma ya nuna ƙimar warkewa. Wadannan cututtuka sau da yawa suna tare da oxidative danniya-induced neuronal lalacewa, kumburi martani, da mitochondrial dysfunction. SS-31, ta hanyar hanyoyi masu yawa irin su daidaita aikin mitochondrial, hana amsawar kumburi, da haɓaka autophagy na salula, yana da alƙawarin jinkirta jinkirin neuronal da kuma inganta alamun haƙuri.
Cututtukan zuciya
Rashin aikin zuciya wani abu ne na gama-gari kuma mai barazanar rayuwa na sepsis. SS-31 yana nuna alamun kariya daga rauni na myocardial a cikin sepsis. A cikin gwaje-gwajen vivo, mice a cikin ƙungiyar masu shiga tsakani na SS-31 sun nuna haɓakar haɓakar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar kuma idan aka kwatanta da ƙungiyar sepsis, da kuma raguwa mai yawa a cikin kwayoyin apoptotic. SS-31 na iya hana haɓakar abubuwan da ke haifar da kumburi a cikin ƙwayar ƙwayar cuta, ƙara yawan abun ciki na ATP, inganta yanayin redox, kula da yiwuwar membrane na mitochondrial, da kuma hana kunna NF-κBp65 da NLRP3, don haka ya rage LPS-induced myocardial rauni. Wannan yana nuna cewa SS-31 na iya zama magani mai yuwuwa don magance cututtukan zuciya da ke haifar da sepsis.
A cikin wasu cututtuka na zuciya da jijiyoyin jini, irin su myocardial ischemia-reperfusion rauni, SS-31 na iya taka muhimmiyar rawa. Tsarin ischemia-reperfusion na myocardial yana haifar da samar da adadi mai yawa na ROS, yana haifar da martani mai kumburi da apoptosis tantanin halitta.
Kammalawa
SS-31 na iya shiga shingen kwakwalwar jini, manufa mitochondria don gyara lalacewar salula, kuma yana da yiwuwar aikace-aikace a cikin cututtuka na jijiyoyin jini, cututtuka na zuciya da jijiyoyin jini, gyaran ƙwanƙwasa ƙwanƙwasa, da ciwon sukari na endothelial rauni. Ta hanyar niyya mitochondria a matsayin ainihin manufa, yana ba da sabuwar ka'idar warkewa.
Sources
[1] Zhu Y, Luo M, Bai X, et al. SS-31, Mitochondria-Targeting Peptide, Ameliorates Kidney Disease[J]. Magungunan Oxidative da Tsawon Rayuwa, 2022,2022:1295509.DOI:10.1155/2022/1295509.
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