Na Cocer Peptides 
30 mau lā aku nei
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 i ʻole maʻi. 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.
Nānā nui
ʻO SS-31, i kapa ʻia ʻo Elamipretide, he peptide cationic aromatic novel. Hiki i ka SS-31 ke hele wale i ka pale koko-lolo, kahi waiwai e kūpono ai no ka mālama ʻana i nā maʻi neurological. ʻO ka pale koko-lolo ka mea he pale pale koʻikoʻi no ka ʻōnaehana nūnū waena, me ka nui o nā lāʻau lapaʻau e hakakā nei. Eia nō naʻe, lanakila ʻo SS-31 i kēia palena, hiki pololei i ke kahua o ka pōʻino neural a hāʻawi i ka manaʻolana no ka hoʻoponopono ʻana i ka pōʻino o ka neural cell. Aia ia i ka papa o nā peptides liʻiliʻi liʻiliʻi, me ke kaupaona haʻahaʻa haʻahaʻa, e hāʻawi iā ia me ka mobility maikaʻi a me ka bioavailability i loko o ke kino. ʻO nā cations i lawe ʻia e SS-31 hiki iā ia ke launa pū me nā mea i hoʻopiʻi maikaʻi ʻole ʻia o nā membrane biological, ʻoi aku ka maikaʻi o nā phospholipid membrane kūloko o ka mitochondria. ʻO kēia paʻa kikoʻī e hiki ai iā SS-31 ke hōʻiliʻili i ka mitochondria, a laila e hoʻokō ai i kāna mau hopena hoʻoponopono i ka hana mitochondrial.
Kiʻi 1 Mechanism o ka hana a SS-31 e kūʻē i ka maʻi kīkī.
Mechanism of Action
Hoʻoponopono i ka hana Mitochondrial
ʻO Mitochondria, ma ke ʻano he mana ikaika o ka cell, he hana koʻikoʻi i ke ola ʻana o ke kelepona a me ka metabolism. ʻO SS-31, me kāna ʻano cationic, hiki ke hōʻiliʻili nui i nā phospholipids membrane i loko o ka mitochondria, a laila e hoʻonui ai i ka hanu mitochondrial. ʻO ke kaulahao hanu mitochondrial kahi ala koʻikoʻi no ka hana ʻana o ka ikehu cellular (ATP). Hoʻonui ka SS-31 i ka hana o nā protein pili i loko o ke kaulahao hanu, hoʻomaikaʻi i ka pono o ka lawe ʻana i ka electron, a laila e hoʻoikaika ana i ka synthesis ATP a hāʻawi i nā cell i ka ikehu kūpono e mālama i nā hana physiological maʻamau e like me ka māhele cell, ka ʻokoʻa, a me ka lawe waiwai.
Hoʻoulu ka SS-31 i ka biogenesis mitochondrial i nā neurons, e hoʻoikaika ana i ka hana o ka mitochondria hou. Ke kū nei nā pūnaewele i ka pōʻino a i ʻole koʻikoʻi, kōkua ka hanauna o ka mitochondria hou e hoʻopiha i ka mitochondria i hōʻino ʻia a i ʻole dysfunctional, e mālama ana i ke olakino o ka heluna mitochondrial i loko o ke kelepona. Hoʻonui ia i ka mitochondrial autophagy, ka mīkini kelepona no ka hoʻomaʻemaʻe ʻana i ka mitochondria i hōʻino ʻia. Inā ʻaʻole hoʻomaʻemaʻe koke ʻia ka mitochondria i pōʻino, hoʻokuʻu lākou i ka nui o nā ʻano oxygen reactive (ROS), ʻoi aku ka pōʻino o nā cell. Hoʻemi maikaʻi ʻo SS-31 i ka hana ROS ma o ka hoʻonui ʻana i ka autophagy mitochondrial, a laila e pale ana i nā cell mai ka pōʻino koʻikoʻi oxidative.
Kāohi i nā pane inflammatory
I loko o nā kaʻina hana pōʻino cellular, hele pinepine nā pane inflammatory i ka pōʻino. ʻO Cytoplasmic phospholipase A2 (cPLA2), ma ke ʻano he mediator mua o ka neuroinflammation, e wāwahi i nā phospholipids membrane ma ke kūlana sn-2 o nā lysosomes ma lalo o nā kūlana pathological, e hana ana i nā lysophospholipids a me ω3 polyunsaturated fatty acids, e alakaʻi ana i ka lysosomal membrane permeabilization (LMP) Hiki i ka SS-31 ke hoʻohaʻahaʻa i ka pae hōʻike o ka phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), kaohi i ka phosphorylation o cPLA2, a laila e hōʻemi ana i ka hana ʻana o nā mea hoʻolaha inflammatory a hoʻēmi i ka pōʻino i hana ʻia e nā pane inflammatory i nā cell.
Ma nā haʻawina e pili ana i kaʻeha myocardial i hoʻokomoʻia i ka sepsis, uaʻikeʻia ka SS-31 e kāohi i ka hoʻouluʻana o NF-κB a me NLRP3, a laila e hoʻomaikaʻi ai i nā pane inflammatory myocardial. ʻO NF-κB kahi mea hoʻoponopono koʻikoʻi o nā ala hōʻailona inflammatory, ʻoiai ʻo NLRP3 kahi mea koʻikoʻi o ka inflammasome. ʻO kā lākou hoʻouluʻana e alakaʻi i ka hoʻokuʻuʻana i ka nui o nā mea inflammatory, e like me IL-6, IL-1β, a me TNF-α. Ma ke kāohi ʻana i ka hoʻoulu ʻana o kēia mau mea koʻikoʻi ʻelua, hōʻemi ʻo SS-31 i nā pae hōʻike o nā mea inflammatory, hoʻēmi i ka pōʻino inflammatory i nā cell myocardial, a mālama i kā lākou hana maʻamau.
Hoʻoulu i ka autophagy a me ka pale ʻana i ka pyroptosis
He mea koʻikoʻi ʻo Autophagy i loko o nā cell e hoʻomaʻemaʻe i nā organelles i hōʻino ʻia, nā protein misfolded, a me nā mea ʻino ʻē aʻe. I nā haʻawina o ka ʻeha spinal cord, ua ʻike ʻia ua hoʻonui ʻo SS-31 i nā pae o nā protein pili autophagy e like me Beclin-1, VPS34, a me LC3, hoʻemi i nā pae o nā protein substrate autophagy e like me p62, akā ʻaʻole pili i nā pae o nā protein pili lysosomal biogenesis e like me ATP6V1B2 a me LAMP1. Hōʻike kēia e hiki i ka SS-31 ke hoʻololi i ka hoʻokumu ʻana o nā autophagosomes ma hope o ka hōʻeha ʻana i ka spinal cord, e like me p62, me ka ʻole o ka hoʻopili ʻana i nā pae o nā protein pili lysosomal biogenesis, e like me ATP6V1B2 a me LAMP1. Hōʻike kēia e hiki i ka SS-31 ke hoʻoikaika i ka hoʻokumu ʻana o nā autophagosome ma hope o ka hōʻeha ʻana i ka spinal cord, hoʻoikaika i ka holomua maʻamau o ke ala autophagy, kōkua i nā cell i ka hoʻomaʻemaʻe ʻana i nā mea i hōʻino ʻia, a hoʻihoʻi i ke kūpaʻa o ke kaiapuni intracellular.
ʻO ka Pyroptosis kahi necrosis programmed inflammatory e alakaʻi ana i ka pōʻino nui o ke kelepona i nā maʻi like ʻole. Hoʻemi ʻo SS-31 i nā kiʻekiʻe o nā protein pili i ka pyroptosis, e like me ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, a me IL-18, a laila e pale ai i ka hiki ʻana o ka pyroptosis. Aia kahi pilina paʻakikī ma waena o autophagy a me pyroptosis; hiki i ka hoʻonui ʻana i ka autophagy ke kāohi i ka pyroptosis. Hoʻoponopono ʻo SS-31 i kēia kaulike, e hōʻemi pono ana i ka make cell ma muli o ka pyroptosis a me ka hoʻoikaika ʻana i ka hoʻoponopono a me ke ola.
Nā noi
Nā maʻi ʻehaʻeha
ʻO ka hōʻeha ʻana i ke kuamoʻo he maʻi hōʻeha koʻikoʻi ia e alakaʻi ana i ka nalowale o ka hana mau a me nā pōʻino kaʻa. Ma muli o ka loaʻa ʻana o ka pale koko-lolo, hakakā nā lāʻau lapaʻau maʻamau e hōʻea i kahi kahua ʻeha. ʻO SS-31, me kona hiki ke hele i ka pale koko-lolo, e hōʻike ana i ka hiki ke hoʻohiki i ka mālama ʻana i ka ʻeha o ke kuamoʻo. I ka lawelawe ʻia ʻana ma o intraperitoneal injection i nā ʻiole me ka ʻeha spinal cord, ua hōʻike ʻia nā loiloi ʻano me ka hoʻohana ʻana i ka pālākiō BMS mouse, ka nānā ʻana i ka gait, a me ka hoʻāʻo mokulele inclined e hoʻoikaika nui i ka hoʻihoʻi ʻana ma hope o ka ʻeha. ʻO ka histologically, me ka hoʻohana ʻana iā HE, Masson, MAP2, a me SYN staining, ua hoʻoholo ʻia ʻo SS-31 e hōʻemi i ka wahi o ka spinal cord glial scarring, hoʻonui i ka helu o nā dendrites a me nā synapses, a hoʻoikaika i ka hoʻoponopono a me ka hana o nā neurons spinal cord.
I nā haʻawina o kekahi mau maʻi neurodegenerative, e like me ka maʻi o Parkinson a me ka maʻi o Alzheimer, ua hōʻike pū ʻo SS-31 i ka waiwai therapeutic kūpono. Hoʻopili pinepine ʻia kēia mau maʻi me ka oxidative stress-induced neuronal damages, inflammatory responses, and mitochondrial dysfunction. ʻO SS-31, ma o nā hana he nui e like me ka hoʻoponopono ʻana i ka hana mitochondrial, ke kāohi ʻana i nā pane inflammatory, a me ka hoʻolaha ʻana i ka autophagy cellular, paʻa i ka ʻōlelo hoʻohiki no ka lohi ʻana i ka degeneration neuronal a me ka hoʻomaikaʻi ʻana i nā hōʻailona maʻi.
Nā maʻi puʻuwai
ʻO ka maʻi puʻuwai he mea maʻamau a hoʻoweliweli i ke ola o ka sepsis. Hōʻike ka SS-31 i nā hopena pale i ka hōʻeha myocardial i ka sepsis. I loko o nā hoʻokolohua vivo, ua hōʻike ʻia nā ʻiole i ka pūʻulu hana SS-31 i hoʻomaikaʻi maikaʻi ʻia ka myocardial tissue disorganization a me ka infiltration inflammatory i hoʻohālikelike ʻia i ka pūʻulu sepsis, a me kahi hōʻemi nui o nā cell apoptotic. Hiki i ka SS-31 ke kāohi i ka upregulation o nā mea inflammatory i loko o ka myocardial tissue, hoʻonui i ka ATP content, hoʻomaikaʻi i ke kūlana redox, mālama i ka pono membrane mitochondrial, a keʻakeʻa i ka hoʻoulu ʻana o NF-κBp65 a me NLRP3, a laila e hoʻohaʻahaʻa i ka ʻeha myocardial i hoʻoiho ʻia e LPS. Hōʻike kēia e lilo paha ʻo SS-31 i lāʻau lapaʻau kūpono no ka mālama ʻana i ka cardiomyopathy i hoʻokomo ʻia i ka sepsis.
I nā maʻi cardiovascular ʻē aʻe, e like me ka myocardial ischemia-reperfusion injury, hiki i ka SS-31 ke pāʻani i kahi hana koʻikoʻi. ʻO ke kaʻina hana myocardial ischemia-reperfusion e alakaʻi i ka hana ʻana o ka nui o ROS, e hoʻoulu ai i nā pane inflammatory a me ka apoptosis cell.
Ka hopena
Hiki i ka SS-31 ke komo i loko o ka pale koko-lolo, ka mitochondria e hoʻoponopono i ka pōʻino o ke kelepona, a loaʻa iā ia nā noi i nā maʻi neurological, nā maʻi maʻi cardiovascular, ka hoʻoponopono ʻana i ka ʻiʻo iwi, a me ka hōʻeha endothelial vascular diabetic. Ma ka huli ʻana i ka mitochondria ma ke ʻano he kumu nui, hāʻawi ia i kahi manaʻo therapeutic hou.
Nā kumu
[1] Zhu Y, Luo M, Bai X, et al. SS-31, he Mitochondria-Targeting Peptide, Hoʻomaikaʻi i ka maʻi ʻōpū [J]. Oxidative Medicine and Cellular Longevity, 2022,2022:1295509.DOI:10.1155/2022/1295509.
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