SS31 50mg

▎ SS-31 Hoʻolālā

▎ ʻImi SS-31

He aha ke kumu noiʻi o SS-31?

ʻO ke kumu noiʻi o SS-31 mai ka ʻike hohonu o ka mitochondrial dysfunction a me nā palena o nā ala lapaʻau e kū nei. He mea koʻikoʻi ka Mitochondria no ka hana kelepona a me ka hana, a pili kā lākou hana ʻole i ka hoʻomaka ʻana a me ka piʻi ʻana o nā maʻi like ʻole, e like me ka maʻi kīkī, nā maʻi neurodegenerative, a me ka pau ʻole o ka naʻau. I kēia mau kūlana, puka mai nā mea ʻino i ka mitochondrial biogenesis, morphology, hana, a me nā loli ikaika, e hana ana i ka mitochondria i mea koʻikoʻi therapeutic target. ʻOiai aia kekahi mau lāʻau lapaʻau i manaʻo ʻia i ka mitochondrial-me nā mea hoʻohui NAD + e like me ka nicotinamide mononucleotide (NMN), ka mitochondrial-targeted pūhui pale ʻo MitoQ, a me ka antioxidant coenzyme Q10 - nā lāʻau lapaʻau kuʻuna e kū nei i nā palena o ka maʻi ma muli o ka maikaʻi ʻole o ka mitochondrial uptake a i ʻole ka make nui. No laila, aia ka pono e hoʻomohala i nā lāʻau lapaʻau ʻoi aku ka maikaʻi.

ʻO ka hemahema o ka naʻau i hoʻoulu ʻia i ke koʻikoʻi kekahi o nā kumu kumu o ka hōʻino ʻana o ka naʻau ma ka honua holoʻokoʻa, me kāna pathophysiology i pili pono i ka mitochondrial dysfunction a me ka myocardial interstitial fibrosis. He mea koʻikoʻi ka ʻike ʻana i nā ala lapaʻau kūpono no ka hoʻomaikaʻi ʻana i nā hopena maʻi. E kū'ē i kēia kua, ua hoʻomohala ka poʻe noiʻi i ka SS-31, kahi antioxidant hou i manaʻo ʻia i ka mitochondrial, e hoʻoponopono i nā pono therapeutic no nā maʻi pili i ka mitochondrial dysfunction. Hoʻohana kūikawā ia i ka membrane mitochondrial i loko, hoʻopaʻa i ke ʻano mitochondrial a me ka hana ʻoiai e hōʻemi ana i ke kaumaha oxidative, e hōʻike ana i ka pono i nā ʻano maʻi he nui.

He aha ka hana o ka SS-31?

Hoʻoponopono i ka hana membrane mitochondrial

Ka launa pū me ka cardiolipin: Hele ʻo Elamipretide i ka membrane mitochondrial waho a hoʻopaʻa iā cardiolipin. ʻO Cardiolipin kahi mea phospholipid koʻikoʻi o ka membrane mitochondrial i loko, e pāʻani ana i kahi kuleana koʻikoʻi i ka mālama ʻana i ke ʻano a me ka hana mitochondrial. Ma o kēia pilina, hoʻomaikaʻi ʻo Elamipretide i ka bioenergetics mitochondrial a me ka morphology. Hōʻike kēia kaʻina hana e like me ka hoʻonui wikiwiki ʻana o ka hana mitochondrial i nā cell stem pluripotent i hoʻokomo ʻia, ʻoi aku hoʻi i nā cell i loaʻa mai nā maʻi me Barth syndrome a me nā cardiomyopathies pediatric hoʻoilina ^[1].

Ke hoʻololi nei i nā waiwai kino membrane: Hōʻike ka noiʻi a Mitchell W e pili ana ʻo Elamipretide me ka lipid bilayer, e hoʻololi ana i nā waiwai kino o ka membrane mitochondrial, ʻoi aku ka nui o nā waiwai electrostatic ma ka interface membrane. Hāʻawi kēia peptide i ka ʻāpana o ka membrane me ka pili a me ka paʻa paʻa i hoʻopili pololei ʻia i ka uku o ka ʻili. ʻOiai ʻaʻole ia e hoʻohaumia i ka lamellar bilayer ma nā ʻano hoʻopaʻa paʻa kiʻekiʻe, hoʻoulu ia i nā loli saturation i ka hoʻopaʻa ʻana o ka lipid, a laila e hoʻopili ai i ka hana membrane mitochondrial ^[2].

Kiʻi 1 Nā mea e pili ana i ka hoʻolako ʻana i ka ikehu puʻuwai a me ke koi ^[1].

Palekana i ka Pūnaehana Nervous

Hoʻonui i ka hana noʻonoʻo: I loko o ka lipopolysaccharide (LPS) i hoʻokomo ʻia i ka ʻiole o ka hōʻino hoʻomanaʻo, ua hoʻomaikaʻi maikaʻi ka mālama ʻana iā Elamipretide i ke aʻo ʻana a me ka hoʻomanaʻo ʻana i ka wai Morris wai maze (MWM) a me nā hoʻāʻo makaʻu wahi. Hiki ke hoʻopili ʻia kēia hopena ameliorative me kona pale ʻana i ka hana mitochondrial, ka hōʻemi ʻana i ke koʻikoʻi oxidative, ka hoʻoponopono ʻana i ke ala hōʻailona neurotrophic factor (BDNF) i loaʻa i ka lolo, a me ka hoʻonui ʻana i ka paʻakikī o ka synaptic. Hoʻohana ka LPS i ka mitochondrial dysfunction, oxidative stress, inflammation, neuronal apoptosis, a me ka dendritic spine loss i ka hippocampus mouse, ʻoiai ʻo Elamipretide i hoʻēmi i kēia mau ʻeha, e hōʻike ana i ka hiki ke pale i ka perioperative neurocognitive dysfunction (PND) ^[3].

Ka hoʻopaʻa ʻana o Neuronal Apoptosis: Ma nā haʻawina hōʻeha spinal cord (SCI), hoʻolaha ʻo Elamipretide i ka hoʻihoʻi ʻana i ka hana ma ke kāohi ʻana i ka pyroptosis, hoʻonui i ka autophagy, a me ka hōʻemi ʻana i ka lysosomal membrane permeability (LMP). Hoʻonui ia i ka autophagy ma ke kāohi ʻana i ka phosphorylation cPLA2 i ka wā e hoʻemi ana i ka pyroptosis a me LMP. No laila, he kuleana koʻikoʻi ʻo Elamipretide i ka hoʻoponopono ʻana i nā hōʻeha neurological ma o ka hoʻoponopono ʻana i nā kaʻina cellular he nui, e hōʻemi ana i ka apoptosis neuronal, a me ka hoʻoulu ʻana i ka hoʻōla hana neural ^[4].

ʻO ke kiʻi 2 Elamipretide (SS-31) i hōʻemi i ke koʻikoʻi oxidative a me ka pane inflammatory i hoʻokomo ʻia e LPS i ka hippocampus mouse. a Reactive oxygen species (ROS), b malondialdehyde (MDA) pae, a me c superoxide dismutase (SOD) hana ^[3].

He aha nā mea hoʻohana o SS-31?

Nā maʻi maʻi neurological

Hoʻomaʻamaʻa ʻana i ka Traumatic Optic Neuropathy: ʻO Traumatic optic neuropathy (TON) hiki ke hoʻopau i ka ʻike maka ma muli o ka trauma orbital blunt. Ua noiʻi nā haʻawina i nā hopena neuroprotective o SS-31 i hui pū ʻia me ka mea necrosis factor (TNF) inhibitor etanercept ma nā retinal ganglion cell (RGCs) ma hope o ka hōʻeha ʻana i ke aʻalolo optic. Tse BC's study me ka hoʻohana 'ana i ka iole ultrasound-induced TON kŘkohu (SI-TON) ua loaʻa i ka intravitreal injection o SS-31 hui me subcutaneous injection o etanercept a me SS-31 nui hoʻonui RGC ola ma 21% (p <0.01) hoʻohālikelike i ka phosphate-buffered saline (PBS) -treated control eyes. Ua hoʻonui ʻia ke ola o RGC me ka 11% (p <0.05) i hoʻohālikelike ʻia me nā mana; ʻO ka subcutaneous injection o etanercept wale nō i hoʻonui i ke ola RGC e 20% (p <0.01) i hoʻohālikelike ʻia i nā mana; ʻO ka subcutaneous injection o SS-31 wale nō i hoʻonui i ke ola RGC e 17% i hoʻohālikelike ʻia i ka pūʻulu mana (p <0.01). Hōʻike kēia mau ʻike i ka hana ʻana o SS-31 i kahi hopena pale i nā RGC i ka mālama ʻana i ka neuropathy optic traumatic, a laila e hoʻomaikaʻi ai i ka acuity ʻike i nā maʻi TON ^[5].

ʻO ka hoʻomaikaʻi ʻana i nā maʻi neurodegenerative pili i ka α-Synuclein: ʻO ka maʻi Parkinson a me nā synucleinopathies pili e pili pono ana me ka paʻa ʻana o ka membrane a me nā waiwai aggregation o α-synuclein. Ua hōʻoia ka noiʻi a Stefaniak e hiki i ka SS-31 ke hoʻololi i nā ʻano ʻāhiu a me N-terminal acetylated α-synuclein mai nā vesicles monolayer liʻiliʻi i hoʻopiʻi maikaʻi ʻia, e kāohi i ka hoʻohui ʻana o ka α-synuclein i hoʻopili ʻia, a hoʻololi i kona morphology fibrillar. Eia kekahi, hoʻihoʻi ʻo SS-31 i ka neʻe ʻana o ka synuclein mai nā vesicles monolayer liʻiliʻi i hoʻopiʻi maikaʻi ʻia, ke kāohi nei i ka hoʻohui ʻana o ka α-synuclein i hoʻokomo ʻia, a hoʻololi i kāna morphology fibrillar. Eia hou, hiki i ka SS-31 ke hoʻihoʻi i ka neʻe ʻana o ka synuclein - mai nā vesicles unilamellar liʻiliʻi i hoʻopiʻi maikaʻi ʻole ʻia, ke kāohi ʻana i ka hoʻohui ʻana o α-SNIP i hoʻokomo ʻia i ka membrane, a hoʻololi i kāna morphology fibrillar. Eia kekahi, ua hoʻihoʻi hou ʻo SS-31 i ka hana mitochondrial impaired i loko o nā cell neuroblastoma i mālama ʻia me nā oligomers α-SNIP a hoʻopaʻa ʻia i ka uptake cellular o kēia mau oligomers. Hōʻike kēia mau ʻike i nā hopena pale multifaceted SS-31 e kūʻē i ka α-synuclein aggregation-induced mitochondrial dysfunction, hoʻonoho iā ia e hoʻēmi i nā maʻi neurodegenerative e pili ana me ka α-synuclein misfolding a me ka hōʻuluʻulu ^[6].

Domain maʻi puʻuwai

Hoʻomaikaʻi i ka hana Mitochondrial i nā poʻe maʻi hōʻino ʻole: ʻike ʻia nā hoʻololi ʻana i ka mitochondrial maikaʻi ʻole i loko o nā maʻi maʻi puʻuwai (HF). Ua mālama nā haʻawina i nā ʻiʻo ventricular ex vivo hou a me ka ʻole o nā keiki a me nā pākeke me SS-31, ke ana ʻana i ka mitochondrial oxygen flux, complex (C) I a me CIV hana, a me ka hana gel-based o ka hui supercomplex. Hōʻike nā ʻike a Chatfield i ka hana mitochondrial impaired i ka hāʻule ʻana o ka naʻau kanaka. Ma hope o ka mālama ʻana i ka SS-31, ka mitochondrial oxygen flux, ka hana CI a me ka CIV, a me ka hana CIV e pili ana i ka hui supercomplex i hoʻomaikaʻi maikaʻi ʻia, e hōʻike ana i ka SS-31 e hoʻomaikaʻi maikaʻi i ka hana mitochondrial i ka hāʻule ʻana o nā naʻau o ke kanaka a hiki ke hoʻopili i ka puʻuwai naʻau ^[7].

Hoʻomaʻamaʻa i ka Barth Syndrome Cardiomyopathy: ʻO ka maʻi Barth kahi maʻi maʻi X-linked a hiki ke make i hōʻike ʻia e ke kiʻekiʻe o ka make pēpē a me ka piʻi ʻana i ka cardiomyopathy me ka hōʻino ʻana o ka ʻōnaehana pale. ʻO SS-31 kahi tetrapeptide e hoʻoheheʻe ʻia i ka wai, aromatic cationic, mitochondrial-targeted tetrapeptide e komo maʻalahi a komo i loko o ka membrane mitochondrial i loko. Hoʻoikaika ia i ke olakino cellular a hoʻopau i ke koʻikoʻi oxidative ma o ka hoʻonui ʻana i ka ikehu a me ke kāohi ʻana i ka hoʻokumu ʻana o nā ʻano oxygen reactive. Hōʻike ka noiʻi Sābbah i ka hoʻomaikaʻi wikiwiki ʻana o SS-31 i ka bioenergetics mitochondrial a me ka morphology i loko o nā puʻupuʻu pluripotent i hoʻokomo ʻia mai nā maʻi me Barth syndrome. Hōʻike ka ʻikepili mai nā ʻano maʻi he nui i ka SS-31 e paʻa i ka ʻōlelo hoʻohiki ma ke ʻano he lāʻau lapaʻau no nā poʻe maʻi me Barth syndrome cardiomyopathy, e hōʻike ana i nā hopena koʻikoʻi i ka poʻe i ʻike ʻia me ka cardiomyopathy. Hiki iā ia ke hana i ka hopena mau loa i ka piʻi ʻana o ka cardiomyopathy aʻo ka hoʻohuli ʻana i ka hoʻoponopono hou ʻana o nā ventricles hema i ka honua, cellular, a me nā pae mole ^[1] .

Musculoskeletal Disease Domain: Hōʻike i ka hiki ke hoʻomaʻamaʻa i ka tendinopathy. Ua hoʻohana ʻo Zhang X i ka ʻiole supraspinatus tendinopathy model, e puʻunaue ana i 126 mau ʻiole (252 lālā) i ʻeono mau pūʻulu hoʻokolohua. Hōʻike nā hualoaʻa mai Zhang X i ka emi ʻana o ka ikaika o ka ʻāʻī ʻana ma hope o ka hopena i hoʻohālikelike ʻia me nā tendon intact. Ua hoʻohuli ʻia kēia hōʻemi ʻana ma hope o ka wehe ʻana i ka paʻi, ka mālama ʻana i ka SS-31, a i ʻole ka lāʻau hui pū, me ka ʻoʻoleʻa e hōʻike ana i ke ʻano like. Ua hōʻike ʻia ka nānā ʻana i ka mōʻaukala i nā helu Bonar i hoʻololi ʻia i ka hui hopena, ʻoiai ka hui pū ʻana i hoʻololi i nā loli morphological i loko o ka tendon. Ua hōʻike ka hui i hoʻopili ʻia i nā helu mitochondrial i hoʻemi ʻia a hoʻololi i ka hui a me ka nui o ka cristae. Ma hope o ka wehe ʻana i ka paʻi a me ka mālama ʻana i ka SS-31, ua hoʻoponopono ʻia ke ʻano mitochondrial a me ka nui, a ua hoʻomaikaʻi ʻia ka morphology cristae. Ua emi ka hana o Superoxide dismutase (SOD) ma hope o ka hopena i hoʻohālikelike ʻia me nā mana akā ua hoʻonui nui ʻia ma hope o ka mālama ʻana, ʻoi aku hoʻi i ka hui hui pū. Ua emi iho ka hōʻike gene pili i ka Mitochondria i ka hui hopena akā ua hoʻi hou ma hope o ka mālama ʻana. Hōʻike kēia i ka SS-31, ma ke ʻano he pale mitochondrial, hoʻomaikaʻi i ka hana mitochondrial a hoʻoikaika i ka ho'ōla ʻana o ka tendon, me ka hoʻonui ʻana i ka pono ke hui pū me ka subacromial impingement removal. Loaʻa iā ia ka hopena therapeutic kūpono no ka supraspinatus tendinopathy [8].

Ka hopena

SS-31 (Elamipretide), ma ke ʻano he mitochondrial-targeted tetrapeptide, hoʻokō i ka pale o ka hana mitochondrial a me ka hoʻoponopono ʻana i nā hōʻeha lehulehu. Hoʻopili ia i ka phosphatidylserine i loko o ka membrane mitochondrial i loko, hoʻopaʻa i ke ʻano o ka membrane a me ka hiki, e hoʻonui ai i ka hana paʻakikī o ka hanu e hoʻoikaika i ka hana ATP, a me ka hoʻomaikaʻi ʻana i ka metabolism ikehu cellular. I ka manawa like, hoʻopau ia i ka hanauna oxygen reactive nui (ROS), hoʻonui i ka hana enzyme antioxidant, a hoʻēmi i ka pōʻino o ke kaumaha oxidative. E pili ana i ka hoʻoponopono inflammatory, kaohi ia i ka NF-κB a me ka NLRP3 inflammasome activation, e hōʻemi ana i ka hoʻokuʻu kumu pro-inflammatory. Hoʻololi ia i nā ala autophagy, hoʻopau i ka apoptosis, a mālama i ka homeostasis mitochondrial ma o nā ala pili. Hāʻawi kēia mau hana i nā hopena maikaʻi i nā maʻi e pili ana i ka dysfunction mitochondrial ma waena o nā ʻōnaehana cardiovascular, neurological, a me musculoskeletal.

No ka mea kakau

ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.

Mea kākau moʻolelo ʻepekema

He mea noiʻi ʻo Kathryn C. Chatfield ma ke Kulanui o Colorado School of Medicine, i hui pū ʻia me nā Keʻena o nā Pediatrics and Medicine / Division of Cardiology. Hoʻopaʻa ʻo ia i ka cardiology pediatric a me ka biology mitochondrial, e noiʻi ana i nā hana i lalo o ka hana naʻau a me nā maʻi. Ua hāʻawi nui ʻo ia i ke kula ma o nā puke naʻauao a me ka hui pū ʻana, a ʻike ʻia kāna hana no ka hoʻonui ʻana i ka ʻike o ka physiology cardiovascular a me nā hoʻolālā lapaʻau kūpono. Ua helu ʻia ʻo Kathryn C. Chatfield ma ka ʻōlelo kuhikuhi [7].

▎ Nā ʻōlelo pili

[1] Sābati HN. ʻO Elamipretide no ka maʻi maʻi maʻi Barth cardiomyopathy: ke kūkulu hou ʻana i kahi pahu mana hāʻule. Nā Manaʻo Hoʻohaʻahaʻa Puʻuwai 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 and Effects on Surface Electrostatics. Biorxiv 2019. https://api.semanticscholar.org/CorpusID:202016574.

[3] Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) hoʻomaikaʻi i ka mitochondrial dysfunction, synaptic a me ka hoʻomanaʻo impairment i hoʻoulu ʻia e ka lipopolysaccharide i nā ʻiole. Nūpepa o Neuroinflammation 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, et al. Hoʻopau ʻo Elamipretide i ka pyroptosis i loko o ke kuamoʻo i hōʻeha ʻia e ka pale ʻana i ka cPLA2-induced lysosomal membrane permeabilization. Nūpepa o Neuroinflammation 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse BC, Dvoriantchikova G, Tao W, et al. Mitochondrial targeted therapy me ka elamipretide (MTP-131) ma ke ʻano he mea hoʻohui i ka necrosis factor inhibition no ka traumatic optic neuropathy i ka hoʻonohonoho koʻikoʻi. Noiʻi maka hoʻokolohua 2020; 199: 108178.DOI:10.1016/j.exer.2020.108178.

[6] ʻO Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Therapeutic Peptide SS-31 Modulates Membrane Paʻa a me ka Hoʻohui ʻana o $alpha$-Synuclein a hoʻihoʻi i ka hana Mitochondrial Impaired. Biorxiv 2024. https://api.semanticscholar.org/CorpusID:271162443.

[7] Chatfield KC, Sparagna GC, Chau S, et al. Hoʻomaikaʻi ʻo Elamipretide i ka hana Mitochondrial i ka naʻau o ke kanaka hāʻule. ʻO 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. ʻO SS-31 ma ke ʻano he Mitochondrial Protectant i ka mālama ʻana i ka Tendinopathy: ʻO ka loiloi i kahi Model Tendinopathy Murine Supraspinatus. Ka Nupepa o ka Iwi a me ka Hui Hoʻopaʻa 'Ai Moku-ʻAmelika Volume 2022; 104(21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.  

ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a maʻi paha. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.