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1 kits (10 Vials)
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▎ Tsarin SS-31
Source: PubChem |
Jerin: RXKF Tsarin kwayoyin halitta: C 32H 49N 9O5 Nauyin Kwayoyin: 639.8g/mol Lambar CAS: 736992-21-5 Saukewa: 11764719 Synonyms: Elamipretide |
▎ SS-31 Bincike
Menene asalin bincike na SS-31?
SS-31 mai narkewa ne mai ruwa, cationic mai kamshi, tetrapeptide mai niyya-mitochondria (Sabbah HN, 2022). Siffar sinadarin sa na musamman yana ba shi damar shiga cikin sauƙi da ɗan gajeren lokaci zuwa ga membrane na mitochondrial na ciki. Musamman, yana iya ɗaure zuwa cardiolipin, babban ɓangaren ƙwayar ƙwayar mitochondrial na ciki, don haka yana yin tasirinsa na inganta aikin mitochondrial.
Wannan keɓantaccen tsarin sinadari yana ba da tushe don aikace-aikacensa wajen magance cututtuka daban-daban. Yawancin cututtuka suna da alaƙa da tabarbarewar mitochondrial, irin su ciwon Barth, raunin zuciya, cututtukan neurodegenerative, da sauransu. Lokacin da aikin mitochondrial ya lalace, yana iya haifar da matsaloli kamar rashin isassun makamashin salula, ƙara yawan damuwa na oxidative, da neuroinflammation, wanda ke haifar da cututtuka daban-daban.
Binciken da ci gaban SS-31 yana da nufin ƙaddamar da waɗannan cututtukan da ke da alaƙa da mitochondrial, rage alamun cututtuka ta hanyar haɓaka aikin mitochondrial da haɓaka ingancin rayuwar marasa lafiya da ƙimar rayuwa. Tare da ci gaba da bincike mai zurfi game da ilimin halitta na mitochondrial, mutane sun fahimci mahimmancin mitochondria a cikin abin da ya faru da ci gaban cututtuka.
Masu bincike sun gano cewa tabarbarewar mitochondrial yana da alaƙa da alaƙa da tsarin ilimin halittar jiki na cututtuka daban-daban. Alal misali, a cikin cututtuka na neurodegenerative, akwai batutuwa irin su rashin aiki na mitochondrial neuronal, neuroinflammation na kullum, tarin sunadarai masu guba, da kuma apoptosis neuronal [1] . Kafin shiga bincike na asibiti, SS-31 ya yi nazari mai zurfi sosai. Waɗannan binciken sun haɗa da gwaje-gwajen da aka gudanar akan samfuran tantanin halitta da samfuran dabbobi don kimanta aminci, inganci, da kaddarorin magunguna na miyagun ƙwayoyi. Alal misali, a cikin nazarin ciwon Barth, SS-31 ya nuna ikon inganta haɓakar ƙwayoyin halittu masu rai da sauri da kuma ilimin halittar jiki a cikin induced pluripotent stem cell model [2].
A cikin bincike game da cututtuka na neurodegenerative, SS-31 ya nuna tasirin neuroprotective a cikin nau'o'in dabba da yawa, ciki har da haɓaka numfashi na mitochondrial, hana neuroinflammation, da kuma hana tarin sunadarai masu guba [1] . SS-31 ya riga ya shiga cikin nazarin asibiti da yawa wanda ya shafi yankunan cututtuka daban-daban.
A cikin maganin cututtukan zuciya, bazuwar, gwajin sarrafa wuribo ya nuna cewa jiko ɗaya na SS-31 yana da aminci kuma yana da jurewa, kuma babban adadin SS-31 na iya haɓaka ƙarar ventricular na hagu, yana tallafawa yuwuwar rawarsa a cikin jiyya na rashin ciwon zuciya [3]..
Menene takamaiman hanyoyin aikin SS-31 a cikin nau'ikan cututtuka daban-daban?
1. Mechanism na aiki a cikin samfurin hemorrhagic shock da aortic balloon occlusion
A cikin misalin raunin ischemia-reperfusion rauni (IRI) wanda ya haifar da bugun jini da bugun jini na aortic (REBOA), lalacewar mitochondrial yana taka muhimmiyar rawa. SS-31 na iya rage buƙatar ruwan crystalloid kuma yana kare kodan da zuciya. Musamman, yana iya rage yawan adadin serum creatinine, troponin, da interleukin-6, amma ba shi da wani tasiri a kan matakin lactate na plasma na ƙarshe. SS-31 na iya rage IRI ta hanyar kare mitochondria, buɗe sabbin hanyoyin magani ga marasa lafiya da ke fama da IRI bayan zubar jini [4].
2. Tsarin aiki a cikin ciwo na Barth
Ciwon Barth wata cuta ce mai alaƙa da X da ba kasafai ba wacce ke da cututtukan zuciya, raunin kwarangwal na tsoka, raguwar girma, da neutropenia na cyclic. SS-31 wani abu ne mai narkewa da ruwa, cationic na kamshi, tetrapeptide mai niyya da mitochondria wanda zai iya shiga cikin membrane na mitochondrial na waje kuma ya ɗaure zuwa cardiolipin. Yana inganta lafiyar kwayar halitta ta hanyar inganta samar da makamashi da kuma hana yawan samuwar nau'in iskar oxygen mai amsawa, ta haka ne ya rage yawan damuwa. A cikin abubuwan da aka jawo pluripotent sel na Barth ciwo da sauran cututtukan da ke da alaƙa da kwayoyin halitta waɗanda ke da cututtukan zuciya na yara, SS-31 na iya haɓaka haɓakar ƙwayoyin cuta da ƙwayoyin cuta da sauri cikin sauri. Sakamakon binciken da yawa yana goyan bayan amfani da SS-31 a matsayin yuwuwar jiyya ga marasa lafiya tare da ciwo na Barth, musamman a lokuta da aka gano cutar cardiomyopathy [2].
3. Mechanism of action in autosomal rinjaye polycystic koda cuta (ADPKD)
An yi la'akari da juna biyu don ƙara ci gaban cysts a cikin cututtukan koda na polycystic na autosomal (ADPKD). Duk da haka, tolvaptan, maganin kawai da FDA ta amince da shi don manya ADPKD, ba a ba da shawarar ga marasa lafiya ADPKD masu ciki ba saboda yuwuwar cutar da tayin. SS-31 shine tetrapeptide mai kariya na mitochondria wanda aka samo don inganta ci gaban cututtukan koda a cikin Pkd1RC / RC mice masu ciki, yayin da rage ERK1 / 2 phosphorylation da inganta samuwar mitochondrial supercomplexes. Bugu da ƙari, SS-31 na iya ƙetare mahaifa da nono nono, inganta 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 cuta ta SS-31 ta SS-31. Waɗannan karatun na yau da kullun suna tallafawa yuwuwar gwajin asibiti na SS-31 [5].
4. Tsarin aiki a cikin gazawar zuciya
A cikin gazawar zuciya (HF), an san canje-canje mara kyau a cikin mitochondria. SS-31 yana da tasiri mai kyau a kan mitochondrial da supercomplex ayyuka na ciwon zuciya na mutum. Yana iya haɓaka haɓakar iskar oxygen, hadaddun I da hadaddun ayyukan IV, da hadaddun ayyukan IV da ke hade da supercomplexes a cikin raunin zuciya mitochondria, inganta haɓaka aikin mitochondrial na ɗan adam [6].
A cikin yara masu fama da cututtukan zuciya guda ɗaya (SV CHD), alamun asibiti don dashen zuciya suna nuna kasancewar rashin aikin mitochondrial. SS-31 wani pentapeptide ne da ke niyya cardiolipin wanda zai iya inganta hulɗar supercomplexes na mitochondrial (complex I, III, IV). A cikin zukatan yara tare da SV CHD, SS-31 na iya inganta hadaddun I ayyuka da matsakaicin numfashi (MR), yana ba da shawarar cewa galibi yana aiwatar da tasirinta ta hanyar haɓaka mitochondrial supercomplexes [7].
5. Hanyar aiki a cikin ciwon sukari nephropathy
A cikin ƙirar linzamin kwamfuta na db/db na nau'in ciwon sukari na 2, ciwon sukari nephropathy (DKD) yana da alaƙa da raguwar matakan superoxide na koda da na zuciya. Wakilin kariyar mitochondria SS-31 (wanda kuma aka sani da MTP-131, SS-31, ko Bendavia) na iya hana haɓakar proteinuria, urinary H₂O₂, da glomerular mesangial matrix tarawa a cikin db/db mice, kuma gaba ɗaya adana matakan samar da superoxide na koda a cikin waɗannan matakan mioxide. SS-31 kuma zai iya rage jimlar lysocardiolipin na renal da kuma manyan nau'o'in lysocardiolipin a cikin db / db mice, da kuma adana maganganun lysocardiolipin acyltransferase 1. Wadannan sakamakon sun nuna cewa a cikin nau'in ciwon sukari na 2, DKD yana hade da raguwa a cikin renal da cardiac superoxide matakan, kuma SS-31 na iya kare kariya daga matakan physigury da DKD. gyare-gyaren cardiolipin [8].
Hoton da aka kwatanta yana taƙaita tasirin neuroprotective na elampretide akan kula da ingancin mitochondria na jijiyoyi.
Source:PubMed [1]
Menene alaƙar aikace-aikacen SS-31?
Cardiomyopathy a cikin Barth ciwo: Barth ciwo ne mai wuya kuma mai yuwuwar cutar da ke da alaƙa da cutar ta X wanda ke da alaƙa da cardiomyopathy, raunin tsoka mai rauni, haɓakar haɓaka, da neutropenia na cyclic. Marasa lafiya suna da babban haɗarin mutuwa a cikin ƙuruciya kuma suna da saurin haɓakar cututtukan zuciya tare da rauni mai ƙarfi na tsarin rigakafi. SS-31 yana gabatar da kalubale da dama don maganin cututtukan zuciya a cikin marasa lafiya tare da ciwo na Barth. Sakamakon binciken da yawa yana goyan bayan amfani da shi azaman yiwuwar jiyya ga marasa lafiya tare da ciwo na Barth, musamman lokacin da aka gano cututtukan zuciya. Yana iya yin tasiri mai ɗorewa akan ci gaban cututtukan zuciya da sannu a hankali da tsarin jujjuyawar gyaran ventricle na hagu na kasawa a duniya, salon salula, da matakan ƙwayoyin cuta [2].
Ciwon zuciya guda ɗaya na ventricle:
Ciwon zuciya da aka haifa shine mafi yawan lahani na haihuwa, kuma mummunan cututtukan zuciya guda ɗaya na haihuwa shine babban alamar dashen zuciyar jarirai, tare da ƙananan hanyoyin magani a halin yanzu. An gano cewa akwai tabarbarewar mitochondrial a cikin zukatan yara masu ciwon zuciya guda ɗaya na ventricle, kuma peptide SS-31 da ke da mitochondria na iya inganta aikin mitochondrial na zuciya. Ƙarin bincike game da ikon wannan magani don inganta aikin zuciya na zuciya da jinkirta ci gaban dasawa ya zama dole [7].
Leber na gado na gani neuropathy:
Wani bincike ya kimanta aminci, juriya, da yuwuwar ingancin amfani da SS-31 a cikin jiyya na marasa lafiya da Leber's hereditary optic neuropathy. Sakamakon ya nuna cewa SS-31 an yi haƙuri da kyau, amma bai kai ga ƙarshen tasirin gani na farko ba. Duk da haka, kimanta aikin gani a lokacin bude-label tsawo tsawo da kuma post-hoc bincike ya nuna ƙarfafawa inganta a cikin ma'ana karkata na tsakiyar gani filin, wanda bukatar ƙarin bincike [9].
Traumatic optic neuropathy:
It has been found that SS-31 (MTP-131), a mitochondria-targeted small molecule tetrapeptide, when used in combination with the tumor necrosis factor inhibitor etanercept, can serve as a neuroprotectant for retinal ganglion cells after optic nerve trauma in mice. Subcutaneous etanercept ko MTP-131 kadai da hadewarsu duk na iya kara yawan rayuwa na kwayoyin ganglion na retinal, amma ba a sami wani tasiri na daidaitawa ba lokacin da aka yi amfani da su a hade [10].
Raunin kashin baya: SS-31 (SS-31) sabon labari ne na peptide mai kamshi wanda zai iya ketare shingen kwakwalwar jini cikin yardar kaina. Nazarin ya nuna cewa SS-31 yana inganta farfadowa na aiki bayan rauni na kashin baya ta hanyar hana cPLA2-matsakaici na autophagic lalacewa, hana karuwa a cikin lysosomal membrane permeability, da kuma hana pyroptosis, kuma yana da yuwuwar ƙimar aikace-aikacen asibiti [11].
Neuroinflammation da rashin fahimta:
A cikin berayen da suka tsufa, lipopolysaccharide na iya haifar da kumburi na tsarin da neuroinflammation, kuma ana iya amfani da SS-31 don magani. Nazarin ya nuna cewa hana haɓakar neuroinflammation na hippocampal ba zai iya rage amsawar kumburi ba kawai a cikin hippocampus amma kuma ya inganta haɗin aikin kwakwalwa a cikin yankuna masu alaƙa da hippocampus. Farkon maganin kumburin kumburi tare da SS-31 yana da tasiri mai dorewa akan rage tasirin lipopolysaccharide-induced neuroinflammation [12].
Autosomal rinjaye polycystic koda cuta:
An yi la'akari da juna biyu don ƙara ci gaban cysts a cikin autosomal rinjaye polycystic koda cuta. An gano cewa mitochondria-protective tetrapeptide SS-31 na iya inganta ci gaban cututtukan koda a cikin Pkd1 ^ {RC/RC} mice mai ciki, yayin da rage ERK1 / 2 phosphorylation da inganta samuwar mitochondrial supercomplexes. SS-31 na iya ƙetare mahaifa da nono nono, inganta mummunan cututtukan koda na polycystic na jarirai ba tare da wani tasirin teratogenic ko cutarwa ba [5].
Cututtukan Neurodegenerative:
SS-31 wani ƙananan ƙwayoyin tetrapeptide ne da aka yi niyya na mitochondria wanda ya nuna tasirin warkewa da aminci a cikin cututtukan da ke da alaƙa da mitochondrial daban-daban. A cikin cututtuka na neurodegenerative, SS-31 na iya haɓaka numfashi na mitochondrial, kunna neuronal mitochondrial biogenesis ta hanyar mitochondrial biogenesis regulators da translocator dalilai, inganta mitochondrial fusion, hana mitochondrial fission, ƙara mitophagy, rage neuronal oxidative danniya, neuroinflammation, da kuma neuronal apoptosis na neuronal survival surutu, neuronal apoptosis. hanyoyi. Sabili da haka, SS-31 na iya hana ci gaban cututtukan neurodegenerative ta hanyar haɓaka mitochondrial respiration, biogenesis, fusion, da hanyoyin rayuwa na neuronal, kazalika da hana mitochondrial fission, damuwa na oxidative, neuroinflammation, tarin sunadarai masu guba, da apoptosis neuronal [1].
Sarcopenia: An gano cewa makonni 8 na jiyya tare da SS-31 na iya jujjuya canje-canjen da suka shafi shekaru a cikin furotin phosphorylation a cikin skeletal tsokoki na tsofaffin mice mata, wanda ya dace da inganta aikin ƙwayar kwarangwal da kuma dawo da canje-canje a cikin furotin S-glutathionylation [13].
A matsayin magungunan mitochondria da aka yi niyya, SS-31 yana ba da sabbin dabarun magance cututtukan mitochondrial. Ta hanyar kare tsari da aikin mitochondria, ya nuna darajar asibiti a cikin cututtuka irin su LHON da Barth ciwo, musamman yana nuna tasiri mai mahimmanci a cikin ƙananan ƙwayoyin cuta na gani. Yana da tasirin warkewa akan cututtuka daban-daban da ke da alaƙa da tabarbarewar mitochondrial, irin su gazawar zuciya da cututtukan neurodegenerative, kuma yana iya sauƙaƙe alamun bayyanar cututtuka da jinkirta ci gaban cutar.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Daneshgar N malami ne mai tasiri a cikin al'ummar ilimi, kuma aikinsa na ilimi yana da alaƙa da Jami'ar Iowa da Jami'ar Jihar Oregon. Filayen bincikensa suna da zurfi kuma suna da zurfi, suna rufe nau'o'i da yawa irin su geriatrics da gerontology, tsarin zuciya da jijiyoyin jini da ilimin zuciya, biochemistry da ilmin kwayoyin halitta, ilmin halitta, da oncology. A fannin ilimin geriatrics da gerontology, Daneshgar N ya himmatu don bincika hanyoyin nazarin halittu na tsufa da ingantaccen aiki don cututtukan da ke da alaƙa da tsufa, yana fatan inganta yanayin rayuwa da matakin lafiyar tsofaffi ta hanyar bincike.
A cikin tsarin tsarin zuciya da jijiyoyin jini, yana gudanar da bincike mai zurfi game da cututtuka, hanyoyin bincike, da kuma hanyoyin magance cututtuka na zuciya da jijiyoyin jini, yana ba da gudummawa ga rigakafi da maganin cututtuka na zuciya. A fannin nazarin halittu da ilmin kwayoyin halitta, ya mayar da hankali kan tsari, aiki, da hulɗar kwayoyin halitta, yana bayyana asirin ayyukan rayuwa a matakin kwayoyin da kuma samar da tushen ka'idar fahimtar cututtuka da magance cututtuka. A cikin fannin ilimin halitta, Daneshgar N yana mai da hankali kan tsari, aiki, da dokokin ayyukan rayuwa na sel, nazarin mahimman matakai irin su siginar siginar tantanin halitta da tsarin sake zagayowar tantanin halitta, yana ba da mahimman alamu don nazarin hanyoyin salula na cututtuka. A fannin ilimin likitanci, ya himmatu wajen gudanar da bincike kan abubuwan da suka faru da hanyoyin ci gaba da ciwace-ciwacen ciwace-ciwacen ciwace-ciwacen daji, da kuma ganowa da kuma kula da ciwace-ciwacen ciwace-ciwacen daji, da binciken alamomin gano wuri da kuma sabbin hanyoyin da za a bi don magance ciwace-ciwacen ciwace-ciwace, wanda ke kawo sabon bege ga masu ciwon daji. An jera Daneshgar N a cikin ambaton ambaton [5].
