SS31 50mg

▎ Tsarin SS-31

▎ SS-31 Bincike

Menene asalin bincike na SS-31?

Binciken bincike na SS-31 ya samo asali ne daga zurfin fahimtar rashin aikin mitochondrial da iyakokin hanyoyin warkewa na yanzu. Mitochondria suna da mahimmanci ga ayyukan salula da aiki, kuma rashin aikin su yana da alaƙa da farawa da ci gaban cututtuka daban-daban, irin su cututtukan koda, cututtukan neurodegenerative, da gazawar zuciya. A cikin waɗannan yanayi, rashin daidaituwa a cikin biogenesis na mitochondrial, ilimin halittar jiki, aiki, da canje-canje masu ƙarfi suna fitowa, suna sa mitochondria ya zama manufa mai mahimmancin warkewa. Kodayake magungunan mitochondrial da yawa sun wanzu-ciki har da abubuwan NAD + kamar nicotinamide mononucleotide (NMN), sigar kariya ta mitochondrial MitoQ, da maganin antioxidant coenzyme Q10-maganin gargajiya suna fuskantar gazawar asibiti saboda rashin haɓakar mitochondrial ko yawan guba. Saboda haka, akwai buƙatu mai mahimmanci don haɓaka ƙarin ingantattun hanyoyin kwantar da hankali.

Rashin ciwon zuciya da ke haifar da damuwa yana wakiltar ɗaya daga cikin manyan abubuwan da ke haifar da gazawar zuciya a duniya, tare da ilimin ilimin halittar jiki wanda ke da alaƙa da rashin aikin mitochondrial da fibrosis na myocardial interstitial. Gano ingantattun hanyoyin warkewa yana da mahimmanci don haɓaka sakamakon haƙuri. A kan wannan yanayin, masu bincike sun haɓaka SS-31, wani sabon abu mai suna mitochondrial-arfafa antioxidant, don magance buƙatun warkewa don cututtukan da ke da alaƙa da mitochondrial. Yana aiki na musamman akan membrane na mitochondrial na ciki, yana daidaita tsarin mitochondrial da aiki yayin da yake rage damuwa na oxidative, yana nuna inganci a cikin nau'ikan cututtuka da yawa.

Menene tsarin aikin SS-31?

Daidaita aikin mitochondrial membrane

Yin hulɗa tare da cardiolipin: Elamipretide ya ketare membrane na mitochondrial na waje kuma yana ɗaure zuwa cardiolipin. Cardiolipin shine mabuɗin phospholipid na membrane na mitochondrial na ciki, yana taka muhimmiyar rawa wajen kiyaye tsarin mitochondrial da aiki. Ta hanyar wannan hulɗar, Elamipretide yana inganta mitochondrial bioenergetics da ilimin halittar jiki. Wannan tsari yana bayyana a matsayin saurin haɓaka aikin mitochondrial a cikin ƙwayoyin sel masu ƙarfi da aka haifar, musamman a cikin sel waɗanda aka samo daga marasa lafiya tare da ciwon Barth da sauran cututtukan cututtukan cututtukan yara na gado ^[1].

Canza kaddarorin jiki na membrane: Binciken Mitchell W ya nuna cewa Elamipretide yana hulɗa tare da bilayer na lipid, yana canza halayen zahiri na membrane na mitochondrial, musamman kaddarorin electrostatic a mahaɗin membrane. Wannan peptide yana rarraba zuwa yankin mu'amalar membrane tare da kusanci da ɗaurin ɗaure kai tsaye da alaƙa da cajin saman. Duk da yake ba ya lalata lamellar bilayer a babban taro mai ɗauri, yana haifar da sauye-sauyen saturation a cikin lipid stacking, don haka yana shafar aikin membrane na mitochondrial ^[2].

Hoto 1 Abubuwan da ke shafar wadatar makamashi da buƙatu na zuciya ^[1].

Kare Tsarin Jijiya

Haɓaka Ayyukan Fahimi: A cikin samfurin linzamin kwamfuta na lipopolysaccharide (LPS) na lalacewar ƙwaƙwalwar ajiya, maganin Elamipretide ya inganta ingantaccen ilmantarwa da ƙwarewar ƙwaƙwalwar ajiya a cikin mashin ruwa na Morris (MWM) da yanayin yanayin gwaji na tsoro. Wannan ingantaccen sakamako na iya haɗawa da kariyar sa na aikin mitochondrial, raguwar damuwa na oxidative, ka'idodin hanyar siginar neurotrophic (BDNF) da aka samu ta kwakwalwa, da haɓaka haɓakar tsarin synaptic. Jiyya na LPS ya haifar da tabarbarewar mitochondrial, damuwa na oxidative, kumburi, apoptosis neuronal, da asarar kashin baya a cikin hippocampus na linzamin kwamfuta, yayin da Elamipretide ya rage waɗannan raunin, yana nuna yuwuwar hana cutar tabarbarewar neurocognitive (PND) ^[3].

Hanawa na Apoptosis na Neuronal: A cikin binciken raunin kashin baya (SCI), Elamipretide yana inganta farfadowa na aiki ta hanyar kawar da pyroptosis, haɓaka autophagy, da rage lysosomal membrane permeability (LMP). Yana haɓaka autophagy ta hanyar hana cPLA2 phosphorylation yayin rage pyroptosis da LMP. Don haka, Elamipretide yana taka muhimmiyar rawa wajen gyara raunin jijiyoyin jiki ta hanyar daidaita tsarin salon salula da yawa, rage apoptosis neuronal, da haɓaka aikin dawo da aikin jijiyoyi ^[4].

Hoto 2 Elamipretide (SS-31) ya rage yawan damuwa na oxidative da amsawar kumburi da LPS ta haifar a cikin hippocampus na linzamin kwamfuta. Matsayin nau'in oxygen mai amsawa (ROS), matakan b malondialdehyde (MDA), da ayyukan c superoxide dismutase (SOD) ^[3].

Menene aikace-aikacen SS-31?

Ciwon Jiki

Treatment of Traumatic Optic Neuropathy: Traumatic optic neuropathy (TON) can cause permanent vision loss due to blunt orbital trauma. Nazarin sun binciki tasirin neuroprotective na SS-31 hade tare da ƙwayar cutar necrosis factor (TNF) inhibitor etanercept akan ƙwayoyin ganglion na retinal (RGCs) bayan raunin jijiya na gani. Tse BC ta binciken ta amfani da linzamin kwamfuta duban dan tayi-jawo TON model (SI-TON) gano cewa intravitreal allura na SS-31 hade da subcutaneous allura na etanercept da SS-31 muhimmanci ƙara RGC rayuwa da 21% (p <0.01) idan aka kwatanta da phosphate-buffered Saline (PBS) kula da idanu. Haɗaɗɗen allurar etanercept da SS-31 sun haɓaka rayuwar RGC da 11% (p <0.05) idan aka kwatanta da sarrafawa; allurar etanercept ta subcutaneous ita kaɗai ta haɓaka rayuwar RGC da 20% (p <0.01) idan aka kwatanta da sarrafawa; Allurar subcutaneous na SS-31 ita kaɗai ta haɓaka rayuwar RGC da 17% idan aka kwatanta da ƙungiyar kulawa (p <0.01). Wadannan binciken sun nuna cewa SS-31 yana yin tasiri mai kariya a kan RGCs a cikin magance cututtukan cututtuka na gani na gani, don haka inganta hangen nesa a cikin marasa lafiya na TON ^[5].

Haɓakawa a cikin α-Synuclein-Related Neurodegenerative Diseases: Cutar Parkinson da synucleinopathies masu alaƙa suna da alaƙa da haɗin kai da haɗin kai na α-synuclein. Binciken Stefaniak ya tabbatar da cewa SS-31 na iya dogaro da dogaro da nau'in nau'in daji da N-terminal acetylated α-synuclein daga mummunan cajin ƙananan ƙwayoyin cuta na monolayer, hana haɓakar α-synuclein da membrane-induced, da canza yanayin halittar fibrillar. Bugu da ƙari kuma, SS-31 yana mayar da ƙaura na synuclein daga ƙananan ƙananan ƙwayoyin cuta na monolayer, yana hana ƙwayar α-synuclein da ke haifar da membrane, kuma ya canza yanayin yanayin fibrillar. Bugu da ƙari, SS-31 na iya mayar da ƙaura na synuclein - daga ƙananan caje-canjen ƙananan unilamellar vesicles, hana ƙwayar α-SNIP da aka haifar da membrane, da kuma canza yanayin halittar fibrillar. Bugu da ƙari kuma, SS-31 ya dawo da aikin mitochondrial na rashin lafiya a cikin ƙwayoyin neuroblastoma da aka bi da su tare da α-SNIP oligomers da kuma katange wayar salula na waɗannan oligomers. Wadannan binciken suna nuna tasirin kariya mai yawa na SS-31 akan α-synuclein aggregation-induced mitochondrial dysfunction, sanya shi don rage cututtukan neurodegenerative da ke hade da α-synuclein misfolding and aggregation ^[6].

Yankin Ciwon Zuciya

Improving Mitochondrial Function in Heart Failure Patients: Adverse mitochondrial alterations are known to exist in heart failure (HF) patients. Nazarin ya bi da sabon ex vivo gazawa da rashin gazawar ventricular nama daga yara da manya tare da SS-31, auna mitochondrial oxygen flux, hadaddun (C) I da CIV ayyuka, da gel-tushen ayyuka na supercomplex taro. Binciken Chatfield ya nuna gazawar aikin mitochondrial a cikin gazawar zukatan mutane. Bayan jiyya na SS-31, mitochondrial oxygen flux, CI da CIV ayyuka, da kuma CIV ayyuka da suka shafi supercomplex taro ya inganta sosai, yana nuna SS-31 yadda ya kamata yana haɓaka aikin mitochondrial a cikin kasawar zukatan ɗan adam kuma yana iya shiga cikin gazawar zuciya ^[7].

Maganin Barth Syndrome Cardiomyopathy: Ciwon Barth cuta ce mai wuyar gaske kuma mai yuwuwar cutar da ke da alaƙa da X wacce ke da yawan mace-macen jarirai da ci gaba zuwa cututtukan zuciya tare da nakasar tsarin rigakafi mai tsanani. SS-31 wani abu ne mai narkewa da ruwa, cationic mai kamshi, tetrapeptide mai niyya na mitochondrial wanda ke shiga cikin hanzari kuma yana ɗan lokaci kaɗan zuwa membrane na mitochondrial na ciki. Yana inganta lafiyar sel kuma yana kawar da damuwa na iskar oxygen ta hanyar haɓaka samar da makamashi da kuma hana yawan samuwar nau'in iskar oxygen. Binciken Sabbah ya nuna cewa SS-31 yana haɓaka haɓakar haɓakar bioenergetics na mitochondrial da ilimin halittar jiki da sauri a cikin ƙwayoyin sel masu ƙarfi waɗanda aka samo daga marasa lafiya tare da Barth syndrome. Bayanai daga nau'ikan cututtuka da yawa suna nuna SS-31 yana ɗaukar alƙawarin azaman yuwuwar jiyya ga marasa lafiya da ke fama da cututtukan cututtukan zuciya na Barth, yana nuna tasirin bayyanannu musamman a cikin waɗanda aka gano tare da cardiomyopathy. Yana iya yin tasiri mai ɗorewa akan ci gaban cardiomyopathy yayin da ake ci gaba da jujjuya tsarin gyaran gyare-gyaren gazawar ventricles na hagu a duniya, salon salula, da matakan ƙwayoyin cuta ^[1] .

Yankin Cuta na Musculoskeletal: Ƙimar da aka nuna a cikin tendinopathy. Nazarin Zhang X ya yi amfani da samfurin supraspinatus tendinopathy na linzamin kwamfuta, inda ya raba ɓeraye 126 (gakaga 252) zuwa ƙungiyoyin gwaji shida. Sakamako daga Zhang X sun nuna cewa ƙarfin karyewar jijiyoyi ya ragu bayan tasiri idan aka kwatanta da jijiyoyi mara kyau. An juyar da wannan raguwa a wani bangare bayan cire manne, jiyya na SS-31, ko hadewar jiyya, tare da taurin yana nuna irin wannan tsari. Binciken tarihi ya nuna mafi girman gyare-gyaren maki Bonar a cikin rukunin tasiri, yayin da haɗin gwiwar jiyya ya sake juyar da sauye-sauyen yanayi a cikin tendon. Ƙungiyar da abin ya shafa ta nuna raguwar lambobi na mitochondrial da canza ƙungiyar cristae da yawa. Bayan cire matsewa da/ko jiyya na SS-31, tsarin mitochondrial da yawa sun daidaita, kuma yanayin halittar cristae ya inganta. Ayyukan Superoxide dismutase (SOD) ya ragu bayan tasiri idan aka kwatanta da sarrafawa amma ya karu da yawa bayan jiyya, musamman a cikin rukunin jiyya na haɗin gwiwa. Maganganun jinsin mitochondria ya ragu a cikin rukunin tasiri amma ya sake dawowa bayan jiyya. Wannan yana nuna cewa SS-31, a matsayin mai kariyar mitochondrial, yana inganta aikin mitochondrial kuma yana inganta warkar da tendon, tare da ingantaccen inganci lokacin da aka haɗa shi tare da cirewar subcromial impingement. Yana riƙe ingantaccen damar warkewa don supraspinatus tendinopathy [8].

Kammalawa

SS-31 (Elamipretide), a matsayin tetrapeptide mai niyya na mitochondrial, yana samun kariyar aikin mitochondrial da gyaran raunin tsarin da yawa. Yana ɗaure zuwa phosphatidylserine a cikin mitochondrial membrane na ciki, daidaita tsarin membrane da yuwuwar, haɓaka hadaddun ayyukan sarkar numfashi don haɓaka samar da ATP, da haɓaka haɓakar kuzarin salula. A lokaci guda, yana hana haɓakar nau'in iskar oxygen mai wuce kima (ROS), yana daidaita ayyukan enzyme na antioxidant, kuma yana rage lalacewar danniya. Game da ƙa'idodin kumburi, yana hana NF-κB da NLRP3 kunnawa mai kumburi, rage sakin abubuwan da ke haifar da kumburi. Yana daidaita hanyoyin autophagy, yana danne apoptosis, kuma yana kula da homeostasis mitochondrial ta hanyoyin da ke da alaƙa. Waɗannan ayyukan suna ba da sakamako masu fa'ida a cikin cututtukan da suka haɗa da tabarbarewar mitochondrial a cikin tsarin zuciya da jijiyoyin jini, jijiyoyin jini, da tsarin musculoskeletal.

Game da Marubuci

Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.

Mawallafin Jaridar Kimiyya

Kathryn C. Chatfield wani mai bincike ne a Jami'ar Colorado School of Medicine, wanda ke da alaƙa da Sashen Ilimin Ilimin Yara da Magunguna / Rarraba Cardiology. Ta mayar da hankali kan ilimin zuciya na yara da ilmin halitta na mitochondrial, bincikar hanyoyin da ke tattare da aikin zuciya da cututtuka. Ta ba da gudummawa mai yawa a fagen ta hanyar wallafe-wallafen masana da haɗin gwiwar, kuma an san aikinta don haɓaka fahimtar ilimin ilimin halittar jini na zuciya da hanyoyin dabarun warkewa. An jera Kathryn C. Chatfield a cikin ambaton ambaton [7].

▎ Abubuwan da suka dace

[1] Sabah HN. Elamipretide don ciwon zuciya na Barth: sake ginawa a hankali na grid mai ƙarfi. Sharhin gazawar Zuciya 2022; 27 (5): 1911-1923.DOI: 10.1007/s10741-021-10177-8.

[2] Mitchell W, Ng EA, Tamucci JD, et al. Tsarin Halitta na Ayyukan Mitochondrial Therapeutic SS-31 (Elamipretide): Ma'amalar Membrane da Tasiri akan Surface Electrostatics. Biorxiv 2019. https://api.semanticscholar.org/CorpusID:202016574.

[3] Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) yana inganta rashin aiki na mitochondrial, rashin lafiyar synaptic da ƙwaƙwalwar ajiya wanda lipopolysaccharide ya haifar a cikin mice. Jaridar Neuroinflammation 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, et al. Elamipretide yana rage pyroptosis a cikin kashin baya mai rauni ta hanyar hana cPLA2-induced lysosomal membrane permeabilization. Jaridar Neuroinflammation 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse BC, Dvoriantchikova G, Tao W, et al. Maganin da aka yi niyya na Mitochondrial tare da elamipretide (MTP-131) a matsayin haɗin kai ga hana ƙwayar cuta necrosis factor don raunin gani neuropathy a cikin matsanancin wuri. Binciken Ido na Gwaji 2020; 199: 108178.DOI:10.1016/j.exer.2020.108178.

[6] Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of $alpha $ -Synuclein and Restore Rage Mitochondrial Action. Biorxiv 2024. https://api.semanticscholar.org/CorpusID:271162443.

[7] Chatfield KC, Sparagna GC, Chau S, et al. Elamipretide Yana Inganta Ayyukan Mitochondrial a Zuciyar Dan Adam da ta Fasa. Jacc-Basic zuwa Kimiyyar Fassara 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 a matsayin Mai Kariyar Mitochondrial a cikin Jiyya na Tendinopathy: Ƙididdiga a cikin Murine Supraspinatus Tendinopathy Model. Jaridar Kashi da Tiyata Haɗin Kai-Ƙarar Ba'amurke 2022; 104 (21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

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 kowane yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.