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1 pahu (10 Vials)
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▎ SS-31 Hoʻolālā
Puna: PubChem |
Kaʻina: RXKF Hui Molekala: C 32H 49N 9O5 Kaumaha Molekala: 639.8g/mol Helu CAS: 736992-21-5 PubChem CID: 11764719 Synonyms: Elamipretide |
▎ ʻImi SS-31
He aha ke kumu noiʻi o SS-31?
ʻO SS-31 kahi wai-soluble, aromatic cationic, mitochondria-targeted tetrapeptide (Sabbah HN, 2022). ʻO kāna ʻano kemika kūʻokoʻa e hiki ai iā ia ke komo maʻalahi a hiki ke hoʻokaʻawale i ka membrane mitochondrial i loko. Ma keʻano kiko'ī, hiki iā ia ke hoʻopaʻa i ka cardiolipin, kahi mea nui o ka membrane mitochondrial i loko, a laila e hoʻoikaika i ka hopena o ka hoʻomaikaʻi ʻana i ka hana mitochondrial.
Hāʻawi kēia ʻano kemika kūʻokoʻa i kumu no kāna noi ʻana i ka mālama ʻana i nā maʻi like ʻole. Nui nā maʻi e pili ana me ka mitochondrial dysfunction, e like me Barth syndrome, heart failure, neurodegenerative maʻi, a me nā mea ʻē aʻe. Ke pilikia ka hana mitochondrial, hiki iā ia ke alakaʻi i nā pilikia e like me ka lawa ʻole o ka ikehu cellular, hoʻonui i ke koʻikoʻi oxidative, a me ka neuroinflammation, ka mea e hoʻoulu ai i nā maʻi like ʻole.
ʻO ka noiʻi a me ka hoʻomohala ʻana o SS-31 e manaʻo e hoʻopaʻa i kēia mau maʻi pili i ka mitochondrial, e hoʻēmi ana i nā hōʻailona maʻi ma o ka hoʻomaikaʻi ʻana i ka hana mitochondrial a me ka hoʻonui ʻana i ka maikaʻi o ke ola a me ka helu ola. Me ka hoʻomau ʻana i ka noiʻi hohonu e pili ana i ka biology mitochondrial, ua ʻike ka poʻe i ke koʻikoʻi o ka mitochondria i ka hanana a me ka ulu ʻana o nā maʻi.
Ua ʻike nā mea noiʻi e pili pono ana ka mitochondrial dysfunction i nā kaʻina pathophysiological o nā maʻi like ʻole. No ka laʻana, i nā maʻi neurodegenerative, aia nā pilikia e like me ka neuronal mitochondrial dysfunction, neuroinflammation mau, ka hōʻiliʻili ʻana o nā protein toxic, a me ka neuronal apoptosis [1] . Ma mua o ke komo ʻana i ka noiʻi lapaʻau, ua hana ʻo SS-31 i nā haʻawina preclinical nui. Ua komo kēia mau haʻawina i nā hoʻokolohua i hana ʻia ma nā hiʻohiʻona cell a me nā ʻano holoholona e loiloi i ka palekana, pono, a me nā waiwai pharmacokinetic o ka lāʻau. No ka laʻana, ma ke aʻo ʻana o Barth syndrome, ua hōʻike ʻo SS-31 i ka hiki ke hoʻomaikaʻi wikiwiki i ka bioenergetics mitochondrial a me ka morphology i nā kumu hoʻohālike pluripotent stem cell [2].
Ma ka noiʻi e pili ana i nā maʻi neurodegenerative, ua hōʻike ʻo SS-31 i nā hopena neuroprotective i nā ʻano holoholona he nui, me ka hoʻonui ʻana i ka hanu mitochondrial, ke kāohi ʻana i ka neuroinflammation, a me ka pale ʻana i ka hōʻiliʻili ʻana o nā protein toxic [1] . Ua komo mua ʻo SS-31 i kekahi mau noiʻi lapaʻau e uhi ana i nā wahi maʻi like ʻole.
I ka mālama ʻana i ka pau ʻole o ka naʻau, ua hōʻike ʻia kahi hoʻokolohua i hoʻopaʻa ʻia i ka placebo i kahi infusion o SS-31 i palekana a ʻae maikaʻi ʻia, a hiki i kahi kiʻekiʻe o SS-31 ke hoʻomaikaʻi i ka volume ventricular hema, e kākoʻo ana i kāna kuleana kūpono i ka mālama ʻana i ka hemahema o ka naʻau [3].
He aha nā hana kūikawā o ka SS-31 i nā ʻano maʻi like ʻole?
1. Mechanism of action in the model of hemorrhagic shock and aortic balloon occlusion
Ma ke kumu hoʻohālike o ka ischemia-reperfusion injury (IRI) i hoʻokumu ʻia e ka hemorrhagic shock a me ka aortic balloon occlusion (REBOA), ʻo ka pōʻino mitochondrial ka mea nui. Hiki i ka SS-31 ke hōʻemi i ka koi no ka wai crystalloid a pale i nā puʻupaʻa a me ka puʻuwai. ʻO ke kikoʻī, hiki iā ia ke hoʻohaʻahaʻa i ka nui o ka serum creatinine, troponin, a me interleukin-6, akā ʻaʻohe hopena i ka hopena lactate plasma hope. Hiki i ka SS-31 ke hoʻohaʻahaʻa i ka IRI ma ka pale ʻana i ka mitochondria, e wehe ana i nā ala lapaʻau hou no nā poʻe maʻi e loaʻa ana i ka IRI ma hope o ke koko [4].
2. Mechanism o ka hana ma Barth syndrome
ʻO ka maʻi ʻo Barth kahi maʻi maʻi X-linked loaʻa i hōʻike ʻia e ka cardiomyopathy, nāwaliwali o ka ʻiʻo iwi, ka lohi o ka ulu ʻana, a me ka neutropenia cyclic. ʻO SS-31 he tetrapeptide hiki ke komo i ka membrane mitochondrial waho a hoʻopaʻa i ka cardiolipin. Hoʻoikaika ia i ke olakino cell ma o ka hoʻomaikaʻi ʻana i ka hana ikehu a me ka pale ʻana i ka hoʻokumu ʻana o nā ʻano oxygen reactive, a laila e hōʻemi ana i ke kaumaha oxidative. I loko o nā pūnaewele pluripotent stem cell o Barth syndrome a me nā maʻi ʻē aʻe e pili ana i ka genetically i hōʻike ʻia e ka cardiomyopathy kamaliʻi, hiki i ka SS-31 ke hoʻomaikaʻi wikiwiki i ka bioenergetics mitochondrial a me ka morphology. Kākoʻo nā hopena o nā haʻawina he nui i ka hoʻohana ʻana i ka SS-31 ma ke ʻano he lāʻau lapaʻau kūpono no nā poʻe maʻi me ka maʻi Barth, ʻoi aku hoʻi i nā hihia i ʻike ʻia ai ka cardiomyopathy [2].
3. Mechanism of action in autosomal dominant polycystic kidney disease (ADPKD)
Manaʻo ʻia ka hāpai ʻana e hoʻonui i ka piʻi ʻana o nā cysts i loko o ka autosomal dominant polycystic kidney disease (ADPKD). Eia nō naʻe, ʻaʻole ʻōlelo ʻia ʻo tolvaptan, ka lāʻau lapaʻau wale nō i ʻae ʻia e ka FDA no ADPKD makua, no ka poʻe maʻi ADPKD hāpai ma muli o ka pōʻino i ka pēpē. ʻO SS-31 kahi tetrapeptide pale mitochondria i ʻike ʻia e hoʻomaikaʻi i ka holomua o ka maʻi maʻi i loko o nā ʻiole Pkd1RC / RC hāpai, ʻoiai e hōʻemi ana i ka phosphorylation ERK1 / 2 a me ka hoʻomaikaʻi ʻana i ke kūkulu ʻana i nā supercomplexes mitochondrial. Eia hou, hiki i ka SS-31 ke hele i ka placenta a me ka waiū umauma, e hoʻomaikaʻi i ka maʻi pēpē polycystic kidney maʻi me ka ʻole o nā hopena teratogenic a i ʻole nā hopena ʻino. Ke kākoʻo nei kēia mau haʻawina preclinical i nā hoʻokolohua lapaʻau kūpono o SS-31 [5].
4. Mechanism o ka hana i ka naʻau hāʻule
Ma ka puʻuwai hāʻule (HF), ʻike ʻia nā loli maikaʻi ʻole i ka mitochondria. He hopena maikaʻi ka SS-31 i ka mitochondrial a me nā hana supercomplex o ka naʻau o ke kanaka. Hiki iā ia ke hoʻonui nui i ka oxygen flux, complex I a me nā hana IV paʻakikī, a me ka hana IV paʻakikī e pili ana me nā supercomplexes i nāwaliwali o ka naʻau mitochondria kanaka, me ka hoʻomaikaʻi nui ʻana i ka hemahema o ka hana mitochondrial kanaka [6].
I nā keiki me ka maʻi puʻuwai congenital ventricle hoʻokahi (SV CHD), hōʻike nā hōʻailona lapaʻau no ka hoʻololi ʻana o ka naʻau i ka hiki ʻana o ka mitochondrial dysfunction. ʻO SS-31 kahi pentapeptide e huli ana i ka cardiolipin hiki ke hoʻomaikaʻi i ka pilina o nā supercomplexes mitochondrial (paʻakikī I, III, IV). I loko o ka puʻuwai o nā keiki me SV CHD, hiki i ka SS-31 ke hoʻomaikaʻi i ka hana paʻakikī I a me ka hanu kiʻekiʻe (MR), e hōʻike ana e hoʻohana nui ia i kona hopena ma ka hoʻomaikaʻi ʻana i nā supercomplexes mitochondrial [7].
5. Mechanism o ka hana ma ka diabetic nephropathy
Ma ke kŘkohu iole db/db o ka ma'i ma'i ma'i type 2, pili ka nephropathy ma'i diabetic (DKD) me ka emi 'ana o ke ki'eki'e o ka renal a me ka cardiac superoxide. Hiki i ka mea hoʻomalu mitochondria SS-31 (i ʻike ʻia ʻo MTP-131, SS-31, a i ʻole Bendavia) ke pale nui i ka piʻi ʻana o ka proteinuria, urinary H₂O₂, a me ka hōʻiliʻili glomerular mesangial matrix i nā ʻiole db/db, a mālama pono i nā pae hana superoxide renal i kēia mau ʻiole. Hiki i ka SS-31 ke ho'ēmi i ka lysocardiolipin renal a me ka lysocardiolipin subclasses nui i nāʻiole db / db, a mālama i ka'ōlelo o ka lysocardiolipin acyltransferase 1. Hōʻike kēia mau hopena i ka maʻi diabetes type 2, pili ka DKD me ka emiʻana o nā kiʻekiʻe supergulat renal a me ka naʻau, a me ka SS-31 a hiki ke pale aku i nā pae supergulating o ka renal a me ka naʻau. cardiolipin remodeling [8].
ʻO ke kiʻikuhi hypothesized e hōʻuluʻulu i nā hopena neuroprotective o ka elamipretide ma ka neural mitochondria quality-control.
Puna:PubMed [1]
He aha nā mea pili o SS-31?
ʻO Cardiomyopathy i ka maʻi maʻi Barth: ʻO ka maʻi ʻo Barth kahi maʻi maʻi X-linked hiki ke hoʻoweliweli i ke ola i hōʻike ʻia e ka cardiomyopathy, nāwaliwali o ka ʻiʻo iwi, ka hoʻihoʻi ʻana o ka ulu, a me ka neutropenia cyclic. Loaʻa i ka poʻe maʻi ka pilikia nui o ka make i ka wā kamaliʻi a hiki ke hoʻomohala i ka cardiomyopathy i hele pū ʻia me ka nāwaliwali nui o ka ʻōnaehana pale. Hōʻike ka SS-31 i nā pilikia a me nā manawa kūpono no ka mālama ʻana i ka cardiomyopathy i nā maʻi me Barth syndrome. Ke kākoʻo nei nā hopena o nā haʻawina he nui i kona hoʻohana ʻana ma ke ʻano he lāʻau lapaʻau kūpono no nā poʻe maʻi me ka maʻi Barth, ʻoiai ke ʻike ʻia ka cardiomyopathy. He hopena mau paha ia i ka piʻi ʻana o ka cardiomyopathy a me ka hoʻohuli ʻana i ka hoʻoponopono hou ʻana o ka ventricle hema i ka honua, cellular, a me nā pae molekala [2].
ʻO ka maʻi puʻuwai congenital ventricle hoʻokahi:
ʻO ka maʻi puʻuwai hānau ka maʻi maʻamau o ka hānau ʻana, a ʻo ka maʻi puʻuwai congenital ventricle koʻikoʻi ka hōʻailona nui no ka hoʻololi ʻana i ka naʻau pēpē, me ka liʻiliʻi loa o nā koho lapaʻau i loaʻa i kēia manawa. Ua ʻike ʻia aia he mitochondrial dysfunction i loko o nā puʻuwai o nā keiki me ka maʻi puʻuwai congenital ventricle hoʻokahi, a hiki i ka mitochondria-targeted peptide SS-31 ke hoʻomaikaʻi i ka hana mitochondrial o ka puʻuwai. Pono ka noiʻi hou aʻe e pili ana i ka hiki o kēia lāʻau lapaʻau e hoʻomaikaʻi i ka hana myocardial a hoʻopaneʻe i ka holomua o ka transplantation e pono ai [7].
ʻO ka neuropathy optic hereditary o Leber:
Ua loiloi ʻia kahi haʻawina i ka palekana, ka hoʻomanawanui, a me ka pono o ka hoʻohana topical o SS-31 i ka mālama ʻana i nā maʻi me ka neuropathy optic hereditary o Leber. Ua hōʻike ʻia nā hopena ua ʻae maikaʻi ʻia ʻo SS-31, akā ʻaʻole i hiki i ka hopena o ka ʻike maka mua. Eia nō naʻe, ʻo ka loiloi ʻana o ka hana ʻike i ka wā o ka wehe ʻana i ka inoa inoa a me ka nānā ʻana i ka post-hoc i hōʻike i ka hoʻoikaika ʻana i ka hoʻomaikaʻi ʻana i ka mean deviation o ke kahua ʻike kikowaena, e koi ana i ka ʻimi hou aku [9].
ʻO ka neuropathy optic traumatic:
Ua ʻike ʻia ʻo SS-31 (MTP-131), kahi mitochondria-targeted liʻiliʻi mole tetrapeptide, ke hoʻohana pū ʻia me ka necrosis factor inhibitor etanercept, hiki ke lilo i neuroprotectant no ka retinal ganglion cell ma hope o ka trauma nerve optic i nā ʻiole. ʻO ka subcutaneous etanercept a i ʻole MTP-131 wale nō a me kā lākou hui pū ʻana hiki ke hoʻonui i ke ola o ka retinal ganglion cell, akā ʻaʻohe hopena synergistic i ʻike ʻia i ka wā i hoʻohana pū ʻia ai [10].
ʻO ka ʻeha o ke kuamoʻo: SS-31 (SS-31) he peptide cationic aromatic hou e hiki ke hele manuahi i ka pale koko-lolo. Ua hōʻike nā haʻawina e hoʻolalelale ʻo SS-31 i ka hoʻihoʻi hou ʻana ma hope o ka hōʻeha ʻana i ka spinal cord ma ke kāohi ʻana i ka cPLA2-mediated autophagic pōʻino, pale i ka piʻi ʻana o ka lysosomal membrane permeability, a me ka pale ʻana i ka pyroptosis, a loaʻa iā ia ka waiwai noiʻi lapaʻau [11].
ʻO ka neuroinflammation a me ka hōʻino ʻana i ka naʻau:
I nā ʻiole kahiko, hiki i ka lipopolysaccharide ke hoʻoulu i ka mumū ʻōnaehana a me ka neuroinflammation, a hiki ke hoʻohana ʻia ka SS-31 no ka mālama ʻana. Ua hōʻike nā haʻawina e hiki ke hoʻohaʻahaʻa i ka neuroinflammation hippocampal wale nō i ka pane ʻana i ka hippocampus akā e hoʻomaikaʻi pū i ka pilina hana o ka lolo ma nā wahi pili i ka hippocampus. ʻO ka hoʻomaʻamaʻa anti-inflammatory mua me SS-31 he hopena mau loa i ka hōʻemi ʻana i ka hopena o ka lipopolysaccharide-induced neuroinflammation [12].
ʻO ka maʻi maʻi polycystic kiʻekiʻe autosomal:
Manaʻo ʻia ʻo ka hāpai ʻana e hoʻonui i ka piʻi ʻana o nā cysts i loko o ka autosomal dominant polycystic kidney maʻi. Uaʻikeʻia e hiki i ka mitochondria-protection tetrapeptide SS-31 ke hoʻonui i ka holomua o ka maʻi maʻi maʻi i loko o nāʻiole Pkd1 ^ {RC / RC} hāpai, i ka ho'ēmiʻana i ka ERK1 / 2 phosphorylation a me ka hoʻomaikaʻiʻana i ke kūkuluʻana i nā supercomplexes mitochondrial. Hiki i ka SS-31 ke hele i ka placenta a me ka waiu waiu, e hoʻomaikaʻi i ka maʻi pēpē polycystic kidney koʻikoʻi me ka ʻole o nā hopena teratogenic i ʻike ʻia [5].
Nā maʻi neurodegenerative:
ʻO SS-31 kahi tetrapeptide liʻiliʻi i hoʻopaʻa ʻia i ka mitochondria i hōʻike i nā hopena therapeutic a me ka palekana i nā maʻi pili i ka mitochondrial. I nā maʻi neurodegenerative, hiki i ka SS-31 ke hoʻoikaika i ka hanu mitochondrial, hoʻoulu i ka neuronal mitochondrial biogenesis ma o ka mitochondrial biogenesis regulators a me nā mea translocator, hoʻonui i ka mitochondrial fusion, ke kāohi i ka mitochondrial fission, hoʻonui i ka mitophagy, hoʻemi i ke koʻikoʻi oxidative neuronal, neuroinflammation, a me ka hōʻiliʻili ʻana o nā protein neuronal a me ke ola ʻana. No laila, hiki i ka SS-31 ke pale i ka piʻi ʻana o nā maʻi neurodegenerative ma o ka hoʻonui ʻana i ka hanu mitochondrial, biogenesis, fusion, a me nā ala ola neuronal, a me ka pale ʻana i ka mitochondrial fission, oxidative stress, neuroinflammation, ka hōʻiliʻili ʻana o nā protein toxic, a me neuronal apoptosis [1].
Sarcopenia: Ua ʻike ʻia ʻo 8 mau pule o ka mālama ʻana me SS-31 hiki ke hoʻololi i nā hoʻololi e pili ana i ka makahiki i ka protein phosphorylation i loko o nā ʻiʻo iwi o nā ʻiole wahine kahiko, i kūlike me ka hoʻomaikaʻi ʻana i ka hana o ka muscle skeletal a me ka hoʻihoʻi ʻana i nā loli i ka protein S-glutathionylation [13].
Ma ke ʻano he lāʻau lapaʻau mitochondria, hāʻawi ʻo SS-31 i kahi hoʻolālā hou no ka mālama ʻana i nā maʻi mitochondrial. Ma ka pale ʻana i ke ʻano a me ka hana o ka mitochondria, ua hōʻike ʻo ia i ka waiwai lapaʻau i nā maʻi e like me LHON a me Barth syndrome, ʻoi aku ka hōʻike ʻana i ka pono nui i ka neuropathy optic acute. Loaʻa ka hopena therapeutic i nā maʻi like ʻole e pili ana i ka mitochondrial dysfunction, e like me ka puʻuwai puʻuwai a me nā maʻi neurodegenerative, a hiki ke hoʻomaha i nā hōʻailona a hoʻopaneʻe i ka piʻi ʻana o ka maʻi.
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 loea koʻikoʻi ʻo Daneshgar N ma ke kaiāulu hoʻonaʻauao, a ua pili pono kāna ʻoihana kula i ke Kulanui o Iowa a me ke Kulanui o Oregon State. Nui a hohonu kāna mau ʻimi noiʻi, e uhi ana i nā ʻano aʻoaʻo like ʻole e like me ka geriatrics a me ka gerontology, cardiovascular system and cardiology, biochemistry and molecular biology, cell biology, and oncology. Ma ke kahua o ka geriatrics a me ka gerontology, ua kūpaʻa ʻo Daneshgar N i ka ʻimi ʻana i nā ʻano hana olaola o ka ʻelemakule a me nā hana kūpono no nā maʻi pili i ka ʻelemakule, me ka manaʻo e hoʻomaikaʻi i ka maikaʻi o ke ola a me ke kūlana olakino o ka poʻe kahiko ma o ka noiʻi.
Ma ke ʻano o ka ʻōnaehana cardiovascular a me ka cardiology, hana ʻo ia i ka noiʻi hohonu e pili ana i ka pathogenesis, nā ala diagnostic, a me nā hoʻolālā mālama o nā maʻi cardiovascular, e hāʻawi ana i ka pale ʻana a me ka mālama ʻana i nā maʻi cardiovascular. Ma ke kahua o ka biochemistry a me ka biology mole, ua kālele ʻo ia i ke ʻano, ka hana, a me ka launa pū ʻana o nā biomolecules, e hōʻike ana i nā mea pohihihi o nā hana ola ma ka pae molekula a hāʻawi i kahi kumu kumu no ka ʻike a me ka mālama ʻana i nā maʻi. Ma ke kahua o ka biology cell, ʻo Daneshgar N ka nānā ʻana i ke ʻano, ka hana, a me nā kānāwai o nā hana ola o nā cell, ke aʻo ʻana i nā kaʻina hana nui e like me ka transduction hōʻailona cell a me ka hoʻoponopono ʻana i ke kinikini cell, e hāʻawi ana i nā hōʻailona koʻikoʻi no ke aʻo ʻana i nā ʻōnaehana kelepona o nā maʻi. Ma ke kahua o ka oncology, ua kūpaʻa ʻo ia i ka noiʻi e pili ana i ka hanana a me ka hoʻomohala ʻana o nā ʻōpū, a me ka ʻike a me ka mālama ʻana i nā ʻōpū, e ʻimi ana i nā māka ʻike mua a me nā pahuhopu therapeutic hou no nā maʻi maʻi, e lawe mai ana i ka manaʻolana hou i nā maʻi maʻi. Ua helu ʻia ʻo Daneshgar N ma ka ʻōlelo kuhikuhi [5].
