SS31 50 mg

▎ SS-31 Qauv

▎ SS-31 Kev Tshawb Fawb

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm SS-31?

Kev tshawb fawb keeb kwm yav dhau los ntawm SS-31 yog los ntawm kev nkag siab tob txog mitochondrial dysfunction thiab cov kev txwv ntawm cov kev kho mob uas twb muaj lawm. Mitochondria yog qhov tseem ceeb rau kev ua haujlwm ntawm tes thiab kev ua haujlwm, thiab lawv qhov kev ua haujlwm tsis zoo cuam tshuam nrog kev pib thiab kev loj hlob ntawm ntau yam kab mob, xws li kab mob raum, neurodegenerative disorders, thiab lub plawv tsis ua haujlwm. Hauv cov xwm txheej no, qhov txawv txav hauv mitochondrial biogenesis, morphology, kev ua haujlwm, thiab kev hloov pauv hloov tau tshwm sim, ua rau mitochondria yog lub hom phiaj kho mob tseem ceeb. Txawm hais tias muaj ntau yam tshuaj mitochondrial-targeted muaj nyob - suav nrog NAD + tshuaj ntxiv xws li nicotinamide mononucleotide (NMN), mitochondrial-targeted tiv thaiv compound MitoQ, thiab cov tshuaj antioxidant coenzyme Q10-cov tshuaj niaj hnub ntsib cov kev txwv kev kho mob vim yog qhov tsis zoo ntawm mitochondrial uptake lossis siab toxicity. Yog li ntawd, muaj kev xav tau los tsim kom muaj txiaj ntsig zoo dua, cov hom phiaj kho.

Kev ntxhov siab vim lub plawv tsis ua haujlwm sawv cev yog ib qho ntawm cov laj thawj tseem ceeb ntawm lub plawv tsis ua haujlwm thoob ntiaj teb, nrog rau nws cov kab mob pathophysiology ze ze rau mitochondrial tsis ua haujlwm thiab myocardial interstitial fibrosis. Kev txheeb xyuas cov txheej txheem kho tau zoo yog qhov tseem ceeb rau kev txhim kho cov txiaj ntsig ntawm tus neeg mob. Tawm tsam qhov teeb meem no, cov kws tshawb fawb tau tsim SS-31, ib qho tshiab mitochondrial-targeted antioxidant, los daws cov kev xav tau kho mob rau cov kab mob mitochondrial tsis ua haujlwm. Nws tshwj xeeb ua rau lub puab mitochondrial membrane, stabilizing mitochondrial qauv thiab muaj nuj nqi thaum txo oxidative kev nyuaj siab, qhia tau hais tias ua tau zoo nyob rau hauv ntau yam kab mob qauv.

Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm SS-31?

Regulating mitochondrial membrane muaj nuj nqi

Kev sib cuam tshuam nrog cardiolipin: Elamipretide hla lub mitochondrial membrane sab nrauv thiab khi rau cardiolipin. Cardiolipin yog ib qho tseem ceeb phospholipid tivthaiv ntawm sab hauv mitochondrial membrane, ua lub luag haujlwm tseem ceeb hauv kev tswj cov qauv mitochondrial thiab kev ua haujlwm. Los ntawm qhov kev cuam tshuam no, Elamipretide txhim kho mitochondrial bioenergetics thiab morphology. Cov txheej txheem no tshwm sim raws li kev txhim kho sai ntawm mitochondrial muaj nuj nqi hauv induced pluripotent qia hlwb, tshwj xeeb tshaj yog nyob rau hauv cov hlwb muab tau los ntawm cov neeg mob nrog Barth syndrome thiab lwm yam noob caj noob ces pediatric cardiomyopathies ^[1].

Kev hloov pauv ntawm daim nyias nyias lub cev: Mitchell W txoj kev tshawb fawb qhia tias Elamipretide cuam tshuam nrog lipid bilayer, hloov kho lub cev lub cev ntawm mitochondrial membrane, tshwj xeeb tshaj yog cov khoom electrostatic ntawm daim nyias nyias. Cov peptide no faib rau thaj tsam ntawm daim nyias nyias nrog affinity thiab binding ceev ncaj qha correlated rau saum npoo. Thaum nws tsis destabilize lub lamellar bilayer ntawm siab binding concentrations, nws induces saturation hloov nyob rau hauv lipid stacking, yog li cuam tshuam rau mitochondrial membrane muaj nuj nqi ^[2].

Daim duab 1 Yam tseem ceeb cuam tshuam rau lub plawv lub zog thiab kev xav tau ^[1].

Kev tiv thaiv lub paj hlwb

Txhim khu kev txawj ntse: Hauv lipopolysaccharide (LPS)-vim nas qauv ntawm kev nco tsis zoo, kev kho Elamipretide tau txhim kho kev kawm thiab kev nco muaj peev xwm hauv Morris dej maze (MWM) thiab cov chaw ntsuas kev ntshai. Cov nyhuv ameliorative no yuav cuam tshuam nrog nws txoj kev tiv thaiv ntawm mitochondrial muaj nuj nqi, txo oxidative kev nyuaj siab, kev tswj ntawm lub hlwb-derived neurotrophic yam (BDNF) taw qhia txoj kev, thiab txhim kho synaptic structural complexity. LPS kev kho mob ua rau mitochondrial dysfunction, oxidative kev nyuaj siab, o, neuronal apoptosis, thiab dendritic spine poob nyob rau hauv nas hippocampus, thaum Elamipretide txo cov kev raug mob no, ua pov thawj muaj peev xwm tiv thaiv perioperative neurocognitive dysfunction (PND) ^[3].

Inhibition of Neuronal Apoptosis: Hauv kev tshawb fawb ntawm tus txha caj qaum (SCI), Elamipretide txhawb kev ua haujlwm rov qab los ntawm kev tawm tsam pyroptosis, txhim kho autophagy, thiab txo qis lysosomal membrane permeability (LMP). Nws txhim kho autophagy los ntawm inhibiting cPLA2 phosphorylation thaum txo cov pyroptosis thiab LMP. Yog li, Elamipretide ua lub luag haujlwm tseem ceeb hauv kev kho cov kev raug mob neurological los ntawm kev tswj hwm ntau cov txheej txheem ntawm tes, txo cov neuronal apoptosis, thiab txhawb kev ua haujlwm ntawm neural rov ua haujlwm ^[4].

Daim duab 2 Elamipretide (SS-31) attenuated oxidative stress thiab inflammatory teb induced los ntawm LPS nyob rau hauv nas hippocampus. ib hom Reactive oxygen (ROS) qib, b malondialdehyde (MDA) qib, thiab c superoxide dismutase (SOD) kev ua ub no ^[3].

Dab tsi yog cov ntawv thov ntawm SS-31?

Neurological Disorders

Kev kho mob ntawm Traumatic Optic Neuropathy: Traumatic optic neuropathy (TON) tuaj yeem ua rau tsis pom kev tas mus li vim muaj kev puas tsuaj ntawm orbital. Cov kev tshawb fawb tau tshawb xyuas cov teebmeem neuroprotective ntawm SS-31 ua ke nrog cov qog necrosis factor (TNF) inhibitor etanercept ntawm cov hlwb hlwb hlwb (RGCs) tom qab raug mob optic paj hlwb. Tse BC txoj kev tshawb fawb siv tus nas ultrasound-induced TON qauv (SI-TON) pom tias intravitreal txhaj ntawm SS-31 ua ke nrog subcutaneous txhaj ntawm etanercept thiab SS-31 ho nce RGC ciaj sia taus los ntawm 21% (p <0.01) piv rau phosphate-buffered saline (PBS). Kev txhaj tshuaj subcutaneous ntawm etanercept thiab SS-31 nce RGC kev ciaj sia los ntawm 11% (p <0.05) piv rau kev tswj hwm; subcutaneous txhaj ntawm etanercept ib leeg nce RGC ciaj sia taus los ntawm 20% (p <0.01) piv rau kev tswj; Kev txhaj tshuaj subcutaneous ntawm SS-31 ib leeg nce RGC ciaj sia los ntawm 17% piv rau pawg tswj hwm (p <0.01). Cov kev tshawb pom no qhia tau hais tias SS-31 ua rau muaj kev tiv thaiv ntawm RGCs hauv kev kho mob optic neuropathy, yog li txhim kho qhov pom kev pom hauv TON cov neeg mob ^[5].

Kev txhim kho hauv α-Synuclein-Related Neurodegenerative Diseases: Parkinson's disease thiab lwm yam synucleinopathies yog zoo sib xws nrog cov membrane binding thiab aggregation zog ntawm α-synuclein. Stefaniak txoj kev tshawb fawb tau lees paub tias SS-31 tuaj yeem siv tshuaj-raws li tshem tawm ob hom tsiaj qus thiab N-terminal acetylated α-synuclein los ntawm qhov tsis zoo them me me monolayer vesicles, inhibit membrane-induced α-synuclein aggregation, thiab hloov nws cov fibrillar morphology. Tsis tas li ntawd, SS-31 rov qab hloov pauv ntawm synuclein los ntawm qhov tsis zoo them me me monolayer vesicles, inhibits membrane-induced α-synuclein aggregation, thiab hloov nws cov fibrillar morphology. Tsis tas li ntawd, SS-31 tuaj yeem kho qhov kev hloov pauv ntawm synuclein - los ntawm qhov tsis zoo them me me unilamellar vesicles, inhibit membrane-induced α-SNIP aggregation, thiab hloov nws cov fibrillar morphology. Tsis tas li ntawd, SS-31 rov qab ua haujlwm tsis zoo mitochondrial hauv cov hlwb neuroblastoma kho nrog α-SNIP oligomers thiab thaiv cov cellular uptake ntawm cov oligomers. Cov kev tshawb pom no qhia txog SS-31's multifaceted tiv thaiv cov teebmeem tiv thaiv α-synuclein aggregation-induced mitochondrial dysfunction, tso nws los txo cov kab mob neurodegenerative cuam tshuam nrog α-synuclein misfolding thiab aggregation ^[6].

Kab mob plawv Domain

Txhim kho Mitochondrial Function nyob rau hauv cov neeg mob plawv tsis ua hauj lwm: Adverse mitochondrial alterations paub tias muaj nyob rau hauv cov neeg mob plawv tsis ua hauj lwm (HF). Cov kev tshawb fawb tau kho tshiab ex vivo tsis ua haujlwm thiab tsis ua haujlwm ventricular cov ntaub so ntswg los ntawm cov menyuam yaus thiab cov neeg laus nrog SS-31, ntsuas mitochondrial oxygen flux, complex (C) I thiab CIV kev ua, thiab gel-raws li kev ua ntawm supercomplex sib dhos. Chatfield qhov kev tshawb pom pom tias muaj kev cuam tshuam mitochondrial ua haujlwm hauv tib neeg lub siab. Tom qab kev kho mob SS-31, mitochondrial oxygen flux, CI thiab CIV kev ua haujlwm, thiab CIV kev ua haujlwm cuam tshuam nrog kev sib dhos supercomplex tau zoo dua qub, qhia tias SS-31 ua tau zoo txhim kho mitochondrial muaj nuj nqi hauv tib neeg lub siab thiab tuaj yeem cuam tshuam rau lub plawv tsis ua haujlwm ^[7].

Kev kho mob ntawm Barth Syndrome Cardiomyopathy: Barth Syndrome yog ib qho tsis tshua muaj thiab muaj peev xwm ua rau tuag taus X-txuas kab mob tshwm sim los ntawm kev tuag ntawm tus menyuam mos siab thiab kev loj hlob mus rau cardiomyopathy nrog kev tiv thaiv kab mob hnyav. SS-31 yog ib qho dej-soluble, aromatic cationic, mitochondrial-targeted tetrapeptide uas nkag tau nkag mus thiab hloov mus rau hauv lub mitochondrial membrane. Nws txhawb nqa cellular noj qab haus huv thiab alleviates oxidative kev nyuaj siab los ntawm kev txhim kho lub zog tsim thiab suppressing ntau reactive oxygen hom tsim. Kev tshawb fawb Sabbah qhia tau hais tias SS-31 sai txhim kho mitochondrial bioenergetics thiab morphology hauv induced pluripotent qia hlwb muab los ntawm cov neeg mob nrog Barth syndrome. Cov ntaub ntawv los ntawm ntau tus qauv kab mob qhia tau hais tias SS-31 tuav cov lus cog tseg raws li txoj kev kho mob rau cov neeg mob uas muaj Barth syndrome cardiomyopathy, uas qhia tau hais tias muaj txiaj ntsig tshwj xeeb hauv cov neeg mob cardiomyopathy. Nws tuaj yeem ua rau muaj kev cuam tshuam ntev rau kev mob plawv cardiomyopathy thaum kev txhim kho cov txheej txheem thim rov qab qhov kev hloov kho ntawm kev ua tsis tiav sab laug ntawm lub ntiaj teb, cellular, thiab qib molecular ^[1] .

Tus Kab Mob Musculoskeletal Domain: Pom tau tias muaj peev xwm kho tau hauv tendinopathy. Zhang X txoj kev tshawb fawb tau siv tus nas supraspinatus tendinopathy qauv, faib 126 nas (252 ceg) ua rau rau pawg sim. Cov txiaj ntsig tau los ntawm Zhang X qhia tias cov leeg pob txha tawg tau txo qis tom qab cuam tshuam piv rau cov leeg tsis muaj zog. Qhov kev txo qis no tau thim rov qab ib nrab tom qab tshem tawm clamp, SS-31 kev kho mob, lossis kev kho ua ke, nrog rau qhov tawv nqaij uas muaj cov qauv zoo sib xws. Kev tshuaj xyuas histological tau qhia txog kev hloov kho Bonar cov qhab nia ntau dua hauv cov pab pawg cuam tshuam, thaum ua ke kev kho mob ib nrab hloov pauv morphological hauv cov leeg. Cov pab pawg cuam tshuam tau nthuav tawm txo cov lej mitochondrial thiab hloov pauv lub koom haum cristae thiab ntom. Tom qab tshem tawm clamp thiab / lossis SS-31 kho, mitochondrial qauv thiab kom muaj nuj nqis normalized, thiab cristae morphology txhim kho. Superoxide dismutase (SOD) kev ua haujlwm tau txo qis kev cuam tshuam tom qab piv rau kev tswj hwm tab sis nce ntxiv tom qab kev kho mob, tshwj xeeb tshaj yog nyob rau hauv kev sib koom ua ke pab pawg. Mitochondria-hais txog cov noob qhia tau txo qis hauv pawg cuam tshuam tab sis rov qab los tom qab kho. Qhov no qhia tau hais tias SS-31, raws li tus tiv thaiv mitochondrial, txhim kho mitochondrial muaj nuj nqi thiab txhawb kev kho cov leeg, nrog txhim kho kev ua tau zoo thaum ua ke nrog subacromial impingement tshem tawm. Nws tuav cov peev xwm kho tau zoo rau supraspinatus tendinopathy [8].

Xaus

SS-31 (Elamipretide), raws li mitochondrial-targeted tetrapeptide, ua tiav mitochondrial muaj nuj nqi tiv thaiv thiab kho ntau qhov kev raug mob. Nws khi rau phosphatidylserine nyob rau hauv lub puab mitochondrial daim nyias nyias, stabilizing daim nyias nyias qauv thiab muaj peev xwm, txhim khu kev ua pa saw complex kev ua si los txhawb ATP zus tau tej cov, thiab txhim kho cellular zog metabolism. Nyob rau tib lub sijhawm, nws inhibits ntau ntau cov pa oxygen hom (ROS) tiam, upregulates antioxidant enzyme kev ua, thiab mitigates oxidative kev nyuaj siab puas. Hais txog kev tswj hwm kev mob nkeeg, nws inhibits NF-κB thiab NLRP3 inflammasome ua kom, txo cov kev tawm tsam ntawm qhov tshwm sim. Nws hloov kho txoj hauv kev autophagy, suppresses apoptosis, thiab tswj mitochondrial homeostasis los ntawm txoj hauv kev. Cov kev ua no ua rau muaj txiaj ntsig zoo hauv cov kab mob uas cuam tshuam nrog kev ua haujlwm ntawm mitochondrial nyob rau hauv cov hlab plawv, paj hlwb, thiab musculoskeletal systems.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Kathryn C. Chatfield yog ib tug kws tshawb fawb ntawm University of Colorado School of Medicine, koom nrog Departments of Pediatrics thiab Medicine/Division of Cardiology. Nws tsom mus rau pediatric cardiology thiab mitochondrial biology, tshawb xyuas cov txheej txheem hauv lub plawv ua haujlwm thiab kab mob. Nws tau pab txhawb ntau yam hauv thaj chaw los ntawm kev tshaj tawm kev tshaj tawm thiab kev sib koom tes, thiab nws txoj haujlwm tau lees paub rau kev nkag siab txog kev mob plawv thiab cov tswv yim kho mob uas muaj peev xwm. Kathryn C. Chatfield tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [7].

▎ Cov Lus Qhia Tseem Ceeb

[1] Sabbah HN. Elamipretide rau Barth syndrome cardiomyopathy: maj mam rov tsim dua ntawm daim phiaj fais fab tuag. Lub plawv Failure Reviews 2022; 27(5): 1911-1923.DOI: 10.1007/s10741-021-10177-8.

[2] Mitchell W, Ng EA, Tamucci JD, et al. Molecular Mechanism of Action of Mitochondrial Therapeutic SS-31 (Elamipretide): Membrane Interactions thiab Effects on Surface Electrostatics. Biorxiv 2019. https://api.semanticscholar.org/CorpusID:202016574.

[3] Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) txhim kho mitochondrial dysfunction, synaptic thiab nco impairment induced los ntawm lipopolysaccharide nyob rau hauv nas. Phau ntawv Journal of Neuroinflamation 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, et al. Elamipretide alleviates pyroptosis hauv traumatically raug mob qaum qaum los ntawm inhibiting cPLA2-induced lysosomal membrane permeabilization. Phau ntawv Journal of Neuroinflamation 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse BC, Dvoriantchikova G, Tao W, et al. Mitochondrial tsom txoj kev kho nrog elamipretide (MTP-131) ua ib qho ntxiv rau cov qog necrosis factor inhibition rau kev puas tsuaj rau cov hlab ntsha hauv qhov chaw mob. Kev Tshawb Fawb Qhov Muag 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 thiab Aggregation of $alpha$-Synuclein thiab Restores Impaired Mitochondrial Function. Biorxiv 2024. https://api.semanticscholar.org/CorpusID:271162443.

[7] Chatfield KC, Sparagna GC, Chau S, et al. Elamipretide Txhim kho Mitochondrial Function hauv Kev Ua Tsis Taus Tib Neeg Lub Plawv. Jacc-Basic to Translational Science 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 raws li Mitochondrial Protectant hauv Kev Kho Mob Tendinopathy: Kev Ntsuas hauv Murine Supraspinatus Tendinopathy Model. Phau ntawv Journal of Bone and Joint Surgery-American Volume 2022; 104(21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.