SS31 50mg

▎ Enzimba ya SS-31

▎ SS-31 Okunoonyereza

Ensibuko y’okunoonyereza eya SS-31 eri etya?

Ensibuko y’okunoonyereza ku SS-31 eva mu kutegeera okw’obwegendereza ku butakola bulungi bwa mitochondria n’obuzibu bw’enkola z’obujjanjabi eziriwo. Mitochondria nsonga nkulu nnyo mu kukola n’okukola kw’obutoffaali, era obutakola bulungi bwazo bukwatagana n’okutandika n’okukulaakulana kw’endwadde ez’enjawulo, gamba ng’endwadde z’ekibumba, obuzibu bw’obusimu obukola emirimu, n’okulemererwa kw’omutima. Mu mbeera zino, obutali bwa bulijjo mu nsengekera y’ebiramu mu mitochondria, enkula, enkola, n’enkyukakyuka ez’amaanyi bivaayo, ekifuula mitochondria ekigendererwa ekikulu eky’obujjanjabi. Newankubadde nga eddagala eriwerako erigendereddwamu mitochondrial liriwo —nga muno mulimu eddagala lya NAD+ nga nicotinamide mononucleotide (NMN), ekirungo ekikuuma ekigendereddwamu mitochondrial MitoQ, ne antioxidant coenzyme Q10 —eddagala ery’ekinnansi lyolekagana n’obuzibu mu bujjanjabi olw’okutwalibwa obubi mu mitochondria oba obutwa obw’amaanyi. N’olwekyo, waliwo obwetaavu obw’amangu okukola obujjanjabi obusingako obulungi, obugendereddwamu.

Okulemererwa kw’omutima okuva ku situleesi kukiikirira ekimu ku bintu ebikulu ebivaako omutima okulemererwa mu nsi yonna, nga pathophysiology yaayo ekwatagana nnyo n’obutakola bulungi bwa mitochondrial ne myocardial interstitial fibrosis. Okuzuula enkola ennungi ez‟obujjanjabi kikulu nnyo mu kulongoosa ebiva mu mulwadde. Mu mbeera eno, abanoonyereza baakola SS-31, ekirungo ekipya ekigenderera mitochondrial-targeted antioxidant, okukola ku byetaago by’obujjanjabi eri endwadde ezeekuusa ku butakola bulungi bwa mitochondrial. Mu ngeri ey’enjawulo kikola ku luwuzi lw’omunda mu mitochondrial, okutebenkeza ensengekera n’enkola ya mitochondrial ate nga kikendeeza ku situleesi y’okwokya, nga kiraga obulungi mu bikolwa by’endwadde eziwera.

Enkola ya SS-31 y’eruwa?

Okulungamya enkola y’oluwuzi lwa mitochondrial

Enkolagana ne cardiolipin: Elamipretide esala oluwuzi lwa mitochondrial olw’ebweru n’ekwatagana ne cardiolipin. Cardiolipin kitundu kya phospholipid ekikulu mu luwuzi lwa mitochondrial olw’omunda, nga kikola kinene nnyo mu kukuuma ensengekera ya mitochondrial n’enkola y’emirimu. Okuyita mu nkolagana eno, Elamipretide erongoosa amaanyi g’ebiramu n’enkula y’ebiramu mu mitochondrial. Enkola eno yeeyolekera ng’okutumbula amangu enkola ya mitochondrial mu butoffaali obusibuka obuyitibwa pluripotent stem cells obuleetebwa naddala mu butoffaali obuva mu balwadde abalina obulwadde bwa Barth syndrome n’obulwadde obulala obw’obusika obw’abaana obw’omutima ^[1]..

Okukyusa eby’obutonde by’olususu: Okunoonyereza kwa Mitchell W kulaga nti Elamipretide ekwatagana ne lipid bilayer, n’ekyusa eby’obutonde eby’oluwuzi lwa mitochondrial naddala eby’amasannyalaze ku nsengekera y’oluwuzi. Peptide eno esaasaanyizibwa mu kitundu ky’ensengekera y’olususu n’enkolagana n’obuzito bw’okusiba ebikwatagana butereevu n’ekisannyalazo eky’okungulu. Wadde nga tekitabangula lamellar bilayer ku high binding concentrations, kireetera saturation enkyukakyuka mu lipid stacking, bwe kityo kikosa mitochondrial membrane function ^[2]..

Ekifaananyi 1 Ensonga ezikwata ku bungi bw’amaanyi g’omutima n’obwetaavu ^[1]..

Okukuuma Enkola y’Obusimu

Enhancing Cognitive Function: Mu lipopolysaccharide (LPS)-induced mouse model of memory impairment, obujjanjabi bwa Elamipretide bwalongoosa nnyo okuyiga n’okujjukira obusobozi mu Morris water maze (MWM) ne conditioned place fear tests. Kino ekikolwa eky’okulongoosa kiyinza okuba nga kikwatagana n’okukuuma kwakyo ku nkola ya mitochondrial, okukendeeza ku situleesi y’okwokya, okulungamya ekkubo ly’obubonero eriva mu bwongo (BDNF), n’okutumbula obuzibu bw’enzimba y’obusimu. Obujjanjabi bwa LPS bwaleeta obutakola bulungi bwa mitochondrial, oxidative stress, okuzimba, neuronal apoptosis, n’okufiirwa dendritic spine mu mouse hippocampus, ate Elamipretide yakendeeza ku buvune buno, nga kiraga obusobozi mu kuziyiza perioperative neurocognitive dysfunction (PND) ^[3]..

Okuziyiza okufa kw’obusimu: Mu kunoonyereza ku buvune bw’omugongo (SCI), Elamipretide etumbula okuddamu okukola ng’eziyiza pyroptosis, okutumbula autophagy, n’okukendeeza ku lysosomal membrane permeability (LMP). Kyongera ku autophagy nga kiziyiza cPLA2 phosphorylation ate nga kikendeeza ku pyroptosis ne LMP. Bwe kityo, Elamipretide ekola kinene nnyo mu kuddaabiriza obuvune bw’obusimu ng’etereeza enkola z’obutoffaali eziwera, okukendeeza ku kufa kw’obusimu, n’okutumbula okuddamu okukola kw’obusimu ^[4]..

Ekifaananyi 2 Elamipretide (SS-31) yakendeeza ku situleesi y’okwokya n’okuddamu kw’okuzimba okuleetebwa LPS mu hippocampus y’ebibe. a Emiwendo gy’ebika bya oxygen ebikola (ROS), b emiwendo gya malondialdehyde (MDA), n’emirimu gya c superoxide dismutase (SOD) ^[3]..

Enkozesa ya SS-31 ze ziruwa?

Obuzibu mu Busimu

Obujjanjabi bw’obulwadde bw’obusimu obuyitibwa Traumatic Optic Neuropathy: Traumatic optic neuropathy (TON) busobola okuleeta okufiirwa okulaba okw’olubeerera olw’okulumwa ennyo mu nkulungo. Okunoonyereza kunonyereza ku bikolwa by’okukuuma obusimu ebya SS-31 nga bigattiddwa wamu n’ekirungo ekiziyiza tumor necrosis factor (TNF) etanercept ku butoffaali bw’amaaso (RGCs) oluvannyuma lw’okulumwa obusimu bw’amaaso. Okunoonyereza kwa Tse BC nga bakozesa enkola ya TON model (SI-TON) eya mouse ultrasound-induced TON model (SI-TON) kwazuula nti empiso ya SS-31 mu vitreal nga egattibwa wamu n’empiso ya etanercept ne SS-31 wansi w’olususu kwayongera nnyo obulamu bwa RGC ebitundu 21% (p < 0.01) bw’ogeraageranya n’amaaso agafuga agajjanjabiddwa phosphate-buffered saline (PBS). Okugatta empiso ya etanercept ne SS-31 wansi w’olususu kwayongera ku bulamu bwa RGC ebitundu 11% (p < 0.05) bw’ogeraageranya n’abafuga; okukuba empiso ya etanercept yokka wansi w’olususu kwayongera ku bulamu bwa RGC ebitundu 20% (p < 0.01) bw’ogeraageranya n’abafuga; Empiso ya SS-31 wansi w’olususu yokka yayongera ku bulamu bwa RGC ebitundu 17% bw’ogeraageranya n’ekibinja ekifuga (p < 0.01). Ebizuuliddwa bino biraga nti SS-31 ekola ekikolwa eky’obukuumi ku RGCs mu kujjanjaba obulwadde bw’obusimu bw’amaaso obulumwa, bwe kityo n’elongoosa okulaba mu balwadde ba TON ^[5]..

Okulongoosa mu α-Synuclein-Related Neurodegenerative Diseases: Obulwadde bwa Parkinson n’obulwadde bwa synucleinopathies obukwatagana nabyo bukwatagana nnyo n’eby’obugagga by’okusiba olususu n’okukuŋŋaanyizibwa kwa α-synuclein. Okunoonyereza kwa Stefaniak kukakasa nti SS-31 esobola okusengula α-synuclein zombi ez’ekika ky’omu nsiko ne N-terminal acetylated okuva mu bikuta ebitono ebirina omusannyalazo omubi, okuziyiza okukuŋŋaanyizibwa kwa α-synuclein okuleetebwa olususu, n’okukyusa enkula yaayo eya fibrillar. Ekirala. Okugatta ku ekyo, SS-31 esobola okuzzaawo okusengulwa kwa synuclein - okuva mu buwundo obutono obwa unilamellar obulina omusannyalazo omubi, okuziyiza okukuŋŋaanyizibwa kwa α-SNIP okuleetebwa olususu, n’okukyusa enkula yaayo ey’obuwuzi. Ekirala, SS-31 yazzaawo enkola ya mitochondria eyakosebwa mu butoffaali bwa neuroblastoma obwajjanjabwa ne α-SNIP oligomers era n’eziyiza obutoffaali okutwala oligomers zino. Ebizuuliddwa bino biraga SS-31’s multifaceted protective effects against α-synuclein aggregation-induced mitochondrial dysfunction, okugiteeka mu kifo okukendeeza ku ndwadde z’obusimu ezikwatagana n’okuzinga obubi n’okukuŋŋaanyizibwa kwa α-synuclein ^[6]..

Ekitundu ky’obulwadde bw’emisuwa

Okulongoosa emirimu gya Mitochondrial mu balwadde abalemererwa omutima: Enkyukakyuka embi mu mitochondria zimanyiddwa nti zibeerawo mu balwadde abalemererwa omutima (HF). Okunoonyereza kwajjanjaba ebitundu by’omusuwa ebipya ebiremereddwa n’ebitalemererwa okuva mu baana n’abantu abakulu abalina SS-31, okupima emisinde gya oxygen flux, complex (C) I ne CIV activity, n’emirimu egyesigama ku gel egy’okukuŋŋaanya supercomplex. Ebizuuliddwa Chatfield biraga okukosebwa kw’enkola ya mitochondria mu mitima gy’abantu egiremereddwa. Oluvannyuma lw’obujjanjabi bwa SS-31, okutambula kwa oxygen mu mitochondrial, emirimu gya CI ne CIV, n’emirimu gya CIV egyekuusa ku kukuŋŋaanyizibwa kwa supercomplex byalongooka nnyo, ekiraga nti SS-31 eyongera bulungi emirimu gya mitochondrial mu mitima gy’abantu egyalemererwa era esobola okuyingira mu kulemererwa kw’omutima ^[7]..

Obujjanjabi bw’obulwadde bwa Barth Syndrome Cardiomyopathy: Obulwadde bwa Barth bulwadde obutatera kulabika era obuyinza okutta obukwatagana ne X obumanyiddwa ng’abaana abawere abafa ennyo n’okukulaakulana okutuuka ku bulwadde bw’emisuwa gy’omutima nga abaserikale b’omubiri bakosebwa nnyo. SS-31 ye tetrapeptide etabulwa mu mazzi, ewunya cationic, mitochondrial-targeted tetrapeptide eyingira mangu era n’ebeera mu kiseera ekitono mu luwuzi lwa mitochondrial olw’omunda. Kitumbula obulamu bw’obutoffaali era kikendeeza ku situleesi y’okwokya (oxidative stress) nga kyongera okukola amaanyi n’okuziyiza okutondebwa kw’ebika bya oxygen ebisukkiridde ebikola. Okunoonyereza kwa Sabbah kulaga nti SS-31 erongoosa mangu amaanyi g’ebiramu n’enkula y’ebiramu mu mitochondrial mu butoffaali obusibuka obuyitibwa induced pluripotent stem cells obuva mu balwadde abalina obulwadde bwa Barth syndrome. Ebiwandiiko okuva mu bikolwa by’endwadde eziwera biraga nti SS-31 esuubiza ng’obujjanjabi obuyinza okuweebwa abalwadde abalina obulwadde bwa Barth syndrome cardiomyopathy, nga bulaga ebikosa naddala mu abo abazuuliddwa n’obulwadde bw’emisuwa gy’omutima. Kiyinza okukola akakwate akawangaala ku kukula kw’obulwadde bw’emisuwa gy’omutima ate nga kigenda kikyusa mu nsengeka y’okuddamu okukola kw’emisuwa gya kkono egyalemererwa ku mutendera gw’ensi yonna, ogw’obutoffaali, ne molekyu ^[1]. .

Ekitundu ky’obulwadde bw’ebinywa n’amagumba: Obusobozi bw’obujjanjabi obwalagibwa mu bulwadde bwa tendinopathy. Okunoonyereza kwa Zhang X kwakozesa enkola ya mouse supraspinatus tendinopathy model, nga kwawulamu ebibe 126 (ebitundu 252) mu bibinja mukaaga eby’okugezesa. Ebivudde mu Zhang X biraga nti amaanyi g’okukutuka kw’emisuwa gakendeera oluvannyuma lw’okukuba bw’ogeraageranya n’emisuwa egitakosebwa. Okukendeera kuno kwakyusibwa ekitundu oluvannyuma lw’okuggyawo clamp, okujjanjaba SS-31, oba obujjanjabi obw’omugatte, ng’obugumu bulaga enkola efaananako bwetyo. Okwekenenya ebitundu by’omubiri kwalaga obubonero bwa Bonar obukyusiddwa obusingako mu kibinja ky’okukosebwa, ate obujjanjabi obw’omugatte bwakyusa ekitundu enkyukakyuka mu nkula y’omusuwa. Ekibinja ekyakosebwa kyalaga okukendeera kw’omuwendo gwa mitochondrial era ne kikyusa ensengeka ya cristae ne density. Oluvannyuma lw’okuggyawo clamp ne/oba okujjanjaba SS-31, ensengekera ya mitochondria n’obungi bwa normalized, era cristae morphology yalongooka. Superoxide dismutase (SOD) activity yakendeera oluvannyuma lw’okukosebwa bw’ogeraageranya n’abafugibwa naye ne yeeyongera nnyo oluvannyuma lw’okujjanjabwa naddala mu kibinja ky’obujjanjabi obw’omugatte. Okwolesebwa kw’obuzaale obukwatagana ne mitochondria kwakendeera mu kibinja ky’okukosebwa naye ne kuddamu okuddamu oluvannyuma lw’okujjanjabwa. Kino kiraga nti SS-31, ng’omukuumi wa mitochondrial, erongoosa enkola ya mitochondrial era etumbula okuwona kw’emisuwa, n’obulungi obw’amaanyi bwe bugattibwa n’okuggyawo subacromial impingement. Kikutte obusobozi obulungi obw’okujjanjaba obulwadde bwa supraspinatus tendinopathy [8].

Mu bufunzi

SS-31 (Elamipretide), nga tetrapeptide egendereddwamu mitochondrial, etuuka ku kukuuma emirimu gya mitochondrial n’okuddaabiriza obuvune mu nkola nnyingi. Kikwatagana ne phosphatidylserine mu luwuzi lw’omunda mu mitochondrial, okutebenkeza ensengekera y’oluwuzi n’obusobozi, okutumbula emirimu gy’olujegere lw’okussa okutumbula okukola ATP, n’okulongoosa enkyukakyuka y’amasoboza g’obutoffaali. Mu kiseera kye kimu, kinyigiriza okutondebwa kw’ebika bya okisigyeni ebisukkiridde (ROS), okulinnyisa emirimu gy’enziyiza y’obuwuka obuziyiza obuwuka obuleeta obulwadde, n’okukendeeza ku kwonooneka kw’okunyigirizibwa okw’okwokya. Ku bikwata ku kulungamya okuzimba, kiziyiza NF-κB ne NLRP3 inflammasome activation, okukendeeza ku pro-inflammatory factor release. Kikyusa amakubo ga autophagy, kinyigiriza apoptosis, era kikuuma mitochondrial homeostasis okuyita mu makubo agakwatagana. Ebikolwa bino biwa ebirungi mu ndwadde ezirimu obutakola bulungi bwa mitochondria mu nkola zonna ez’emisuwa, obusimu, n’ebinywa n’amagumba.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Kathryn C. Chatfield munoonyereza mu Yunivasite y’e Colorado School of Medicine, eyeegatta ku Departments of Pediatrics and Medicine/Division of Cardiology. Essira aliteeka ku by’omutima gw’abaana n’ebiramu ebiyitibwa mitochondrial biology, ng’anoonyereza ku nkola ezisibukako omutima okukola n’endwadde. Akoze kinene mu mulimu guno ng’ayita mu bitabo by’abayivu n’okukolagana, era omulimu gwe gumanyiddwa olw’okutumbula okutegeera kw’enkola y’emisuwa gy’omutima n’obukodyo obuyinza okujjanjaba. Kathryn C. Chatfield awandiikiddwa mu kiwandiiko ekijuliziddwa [7].

▎ Ebiwandiiko Ebikwatagana

[1] Ssabbiiti HN. Elamipretide for Barth syndrome cardiomyopathy: okuddamu okuzimba mpolampola omukutu gw’amasannyalaze ogwalemererwa. Okuddamu okwetegereza ku kulemererwa kw’omutima 2022; 27 (5): 1911-1923.DOI: 10.1007/s10741-021-10177-8.

[2] Mitchell W, Ng E. A., Tamucci J. D., n’abalala. Enkola ya molekyu y’okukola kwa Mitochondrial Therapeutic SS-31 (Elamipretide): Enkolagana y’olususu n’ebikosa ku masanyalaze ag’okungulu. Biorxiv 2019. Enkola y’okukuuma obutonde bw’ensi mu bitundu by’eggwanga eby’enjawulo.

[3] Zhao W, Xu Z, Cao J, n’abalala. Elamipretide (SS-31) erongoosa obutakola bulungi bwa mitochondrial, okukosebwa kw’obusimu n’okujjukira obuva ku lipopolysaccharide mu mbeba. Journal of Obuzimba bw’obusimu 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, n’abalala. Elamipretide ekendeeza ku pyroptosis mu mugongo ogufunye obuvune ng’eziyiza cPLA2-induced lysosomal membrane permeabilization. Journal of Obuzimba bw’obusimu 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse B. C., Dvoriantchikova G, Tao W, n’abalala. Mitochondrial targeted therapy ne elamipretide (MTP-131) nga adjunct ku tumor necrosis factor inhibition ku traumatic optic neuropathy mu mbeera ey’amangu. Okunoonyereza ku maaso mu kugezesa 2020; 199: 108178.DOI:10.1016/j.exer.2020.108178.

[6] Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Peptide SS-31 ey’obujjanjabi ekyusa okusiba n’okukuŋŋaanyizibwa kw’olususu lwa $alpha$-Synuclein era n’ezzaawo emirimu gya Mitochondrial egyakosebwa. Biorxiv 2024. Enkola y’okukuuma obutonde bw’ensi mu bitundu by’eggwanga eby’enjawulo.

[7] Chatfield KC, Sparagna G. C., Chau S., n’abalala. Elamipretide Alongoosa Enkola Ya Mitochondrial mu Mutima gw’Omuntu ogulemererwa. Jacc-Basic mu Sayansi w’Okuvvuunula 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 S. A., ne bannaabwe abalala. SS-31 nga Mitochondrial Protectant mu kujjanjaba Tendinopathy: Okukebera mu Murine Supraspinatus Tendinopathy Model. Journal of Okulongoosa amagumba n’ennyondo-American Volume 2022; 104 (21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.