Cocer Peptides ye 
ŋlɔe ɣleti 1 enye sia
NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.
Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.
Melanotan-II ƒe Kpɔɖeŋu
Melanotan-II (MT-II) nye α-melanocyte-stimulating hormone (α-MSH) ƒe nɔnɔmetata si wowɔ si le melanocortin agonists ƒe hatsotso me. Menye nusiwo do ƒome kple lãgbalẽ ɖeɖekoe wozãna na MT-II o; le atikewɔwɔ ŋuti numekuku me la, wole eŋu bum be woate ŋu azãe le nɔnɔmewo abe tsitretsitsi ƒe dɔmawɔmawɔ nyuie ene dada me hã.
Nɔnɔmetata 1 Melanotan-II ƒe wɔwɔme.
Melanotan-II Dɔwɔwɔ ƒe Mɔnu
MT-II wɔa eƒe ŋusẽkpɔɖeamedziwo koŋ to nuwɔwɔ kple melanocortin receptors (MCRs) me. Melanocortin xɔla ƒe ƒomea lɔ ƒomevi sue geɖewo abe MC1R, MC2R, MC3R, MC4R, kple MC5R ene ɖe eme. MT-II nye melanocortin receptor agonist si metiaa ame o si ate ŋu abla ɖe MCR geɖe ŋu eye wòana woawɔ dɔ.
Le ŋutigbalẽ me la, MT-II blana ɖe MC1R ŋu le melanocytes ƒe anyime, si wɔnɛ be adenylate cyclase wɔa dɔ, si dzia cyclic AMP (cAMP) ƒe agbɔsɔsɔ ɖe edzi, si wɔnɛ be protein kinase A (PKA) wɔa dɔ. PKA naa microphthalmia-associated transcription factor (MITF) wɔa dɔ to phosphorylation dzi. MITF nye nuŋɔŋlɔ ƒe akpa vevi aɖe le melanin ƒe wɔwɔme me, Edoa domenyiŋusẽfianuwo abe tyrosinase, tyrosinase-related protein-1 (TRP-1), kple tyrosinase-related protein-2 (TRP-2), siwo nye enzyme siwo kpɔa gome le melanin ƒe wɔwɔme me ƒe ɖeɖefia ɖe dzi, si wɔnɛ be ŋutigbalẽ ƒe amadede dzina ɖe edzi mlɔeba eye wòkpɔa ŋutigbalẽ ƒe amadede ƒe ŋusẽkpɔɖeamedzi.
Le lãmekawo me la, MT-II kpɔa ŋusẽ ɖe ahɔhɔ̃meka aɖewo hã dzi. Ate ŋu aʋã oxytocin ƒe ɖoɖo si le titina. Numekukuwo ɖee fia be MT-II dodo ɖe ʋuka me naa Fos ƒe ɖeɖefia le ahɔhɔ̃meka gãwo me le suprachiasmatic nucleus (SON) kple paraventricular nucleus (PVN) si le hypothalamus me vevie, si nye ŋuɖoɖo si woate ŋu aɖe akpɔtɔ to melanocortin ƒe mɔxenu SHU-9119 dodo ɖe ahɔhɔ̃mekawo me do ŋgɔ me. Elektrikŋusẽ ŋuti nuŋlɔɖiwo ɖee fia be MT-II dodo ɖe ʋuka me dzia oxytocin ahɔhɔ̃meka siwo le SON me ƒe tudada zi gbɔ zi geɖe ɖe edzi gake meʋãa dendritic oxytocin ƒe dodo le SON me o. Le numekuku siwo wowɔ va yi siwo ɖee fia be melanocortin agonists zazã tẽ xea mɔ na supraoptic nucleus (SON) oxytocin neurons ta la, MT-II si wodona ɖe ʋuka me ƒe ŋusẽkpɔɖeamedziwo ate ŋu anye domenɔla ƒe akpa aɖe ya teti le mɔ si mele tẽ o nu, si ate ŋu anye to nusiwo wotsɔ dea ahɔhɔ̃meka me ƒe dɔwɔwɔ me, afisi MT-II hã dzia Fos ƒe ɖeɖefia ɖe edzi le.
Tsɔ kpe ɖe eŋu la, mɔnu aɖewo le MT-II si wɔa dɔ ɖe ŋusẽ ƒe asitɔtrɔ kple dzoxɔxɔ ƒe ɖoɖowɔwɔ dzi. Le sisiblisiwo ƒe dodokpɔwo me la, MT-II dodo ɖe dɔgboa me naa lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe ɖiɖi/dzoxɔxɔ si nu sẽna ɖedzesi si nɔa anyi ɣeyiɣi kpui aɖe ko. Nudzɔdzɔ sia si me dzoxɔxɔ nu sẽna la nu yina le Kit W-sh/W-sh mice siwo si mast cells mele o me, si fia be mast cells le vevie na dzoxɔxɔ si MT-II hena vɛ. MT-II ate ŋu aʋã mast cells to mɔnu siwo nɔa te ɖe MRGPRB2 dzi kple esiwo mele wo ɖokui si o siaa dzi be woaɖe histamine, si naa dzoxɔxɔ si nu sẽ to histamine H 1 xɔlawo dzi, elabena mɔxenu tiatia si nye pyrilamine alo H 1 xɔlawo ɖeɖeɖa ɖea dzoxɔxɔ ƒe ŋusẽkpɔɖeamedzi sia dzi kpɔtɔna ŋutɔ.
Melanotan-II ƒe ŋusẽkpɔɖeamedzi
Akpa si Wòwɔna Le Ŋutilã ƒe Amadede Me
MT-II ƒe ŋusẽkpɔɖeamedzi ɖedzesitɔwo dometɔ ɖekae nye be wònana ŋutigbalẽ ƒe amadede nadzi ɖe edzi, si fia be, eƒe ŋutigbalẽ ƒe amadede nana ame ƒe ŋutigbalẽ ƒe amadede nadzi ɖe edzi. Nyaŋuɖoɖo tso ezãlawo gbɔ ɖee fia be gomekpɔla siwo katã kloe te lãgbalẽŋudɔdada kpɔ kple MT-II ɖe ŋutigbalẽ ƒe viviti fia. Esia ɖee fia be MT-II le eɖokui si vaseɖe afi aɖe le ŋutigbalẽ ƒe amadede hehe vɛ me, menɔ te ɖe ultraviolet keklẽ dzi bliboe be wòadze melanogenesis mɔ̃a gɔme o.Le numekuku aɖewo me la, ŋkuléle ɖe lãwo ƒe kpɔɖeŋuwo kple lãmenugbagbeviwo dodokpɔ siwo wowɔ le vitro me ɖee fia be MT-II doa ŋusẽ melanocytes tẽ, si naa enzymes wɔwɔ si do ƒome kple melanin ƒe wɔwɔme ƒe ɖeɖefia dzina ɖe edzi, to esia me doa melanin kple viviti dodo ɖe ŋgɔ ŋutigbalẽ ƒe amadede. Dɔwɔwɔ sia nyea mɔnu bubu si ate ŋu ana amesiwo le akɔbli ƒe ŋutigbalẽ dim esime wole dzi tsim ɖe ŋutigbalẽ ƒe gbegblẽ si UV hena vɛ ŋu.
Ŋusẽkpɔɖeamedzi ɖe Ahɔhɔ̃mekawo ƒe Nuwɔna Dzi
Le ahɔhɔ̃mekawo ƒe nuwɔna ƒe ŋusẽkpɔɖeamedzi gome la, MT-II ɖea nuwɔna siwo le go geɖe me fiana. Le numekuku siwo wowɔ tsɔ zã sɔmelãwo abe kpɔɖeŋu ene me la, wokpɔe be ɣeyiɣi kpui aɖe ƒe nuɖuɖu siwo me ami sɔ gbɔ ɖo (HF) gɔ̃ hã (si nɔa anyi abe sɔmelã ƒe agbenɔƒe ƒe 1% ko, alo kwasiɖa etɔ̃) ate ŋu ana ame ƒe ŋkuɖoɖonudzi ƒe dzesidede nu nagbɔdzɔ, dzimaɖitsitsi ƒe agbɔsɔsɔ nadzi ɖe edzi, eye wòana didi ƒe didi dzi naɖe akpɔtɔ le sɔmelãwo me. MT-II ate ŋu atrɔ asi le nusiwo mesɔ o siawo siwo nuɖuɖu si me ami sɔ gbɔ ɖo hena vɛ ŋu, si ana zebrafish ƒe ŋkuɖoɖonudzi, dzimaɖitsitsi, kple numekuku ƒe nuwɔna nagaɖo eƒe agbɔsɔsɔ si sɔ kple nuɖuɖu si sɔ ƒe ƒuƒoƒoa tɔ.
Le numekuku siwo ku ɖe autism ŋu me la, wozã vidada ƒe dɔlélenutsiŋutete ƒe dɔwɔwɔ (MIA) ƒe sisiblisi ƒe kpɔɖeŋu tsɔ srɔ̃ autism ƒe kpɔɖeŋu la, MIA mice ŋutsuwo ɖea nɔnɔme siwo le abe autism ene fiana, abe hadomenuwɔna ƒe dzesi siwo gblẽ, gbeɖiɖi ƒe kadodo dzi ɖeɖe kpɔtɔ, kple nuwɔna siwo gbugbɔna gblɔna ƒe dzidziɖedzi ene. Le MT-II zazã ŋkeke adre megbe la, hadomenuwɔna ƒe dzesiwo nyo ɖe edzi le MIA mice ŋutsuwo me, gake hadomenuwɔna ƒe dzesiwo le C57 mice siwo ƒe nɔnɔme sɔ me meɖe tɔtrɔ gã aɖeke fia le MT-II zazã vɔ megbe o. Esia fia be MT-II ate ŋu akpɔ ŋusẽ ɖe atikewɔwɔ dzi le nuwɔna ƒe gbɔdzɔgbɔdzɔ siwo le abe autism ene ƒe nyonyo me, si naa mɔfiame yeyewo na autism dada ŋuti numekuku.
Nɔnɔmetata 2 MIA mice ŋutsu tsitsiwo ɖe oxytocin receptor ƒe ɖeɖefia ƒe dzidziɖedzi fia le anterior cingulate cortex me.
Ŋusẽkpɔɖeamedzi ɖe ŋusẽ ƒe asitɔtrɔ kple dzoxɔxɔ ƒe ɖoɖowɔwɔ dzi
MT-II kpɔa ŋusẽ gã aɖe ɖe ŋusẽ ƒe asitɔtrɔ kple dzoxɔxɔ ƒe ɖoɖowɔwɔ hã dzi. Le sisiblisiwo ƒe dodokpɔwo me la, wodo MT-II na sisiblisi siwo ŋu pituitary adenylate cyclase-activating peptide (PACAP) mele o to atike si wodona ɖe wo ŋu me gbesiagbe kwasiɖa etɔ̃ tsiã ɖe enu le vuvɔ ƒe tɔtrɔ ɖe nɔnɔme ŋu me. Nusiwo do tso eme ɖee fia be MT-II ate ŋu agbugbɔ dzoxɔxɔ ƒe ŋutete si gblẽ le sisiblisiwo ŋu ƒe akpa aɖe aɖo anyi. To lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe agbɔsɔsɔ si norepinephrine hena vɛ dzidzedze me la, wokpɔe be dzoxɔxɔ ƒe ŋutete si le sisiblisi siwo wotsɔ MT-II da dɔe ŋu la gaɖo eƒe akpa aɖe. Tsɔ kpe ɖe eŋu la, MT-II dɔdamɔnu ɖɔ gbɔdzɔgbɔdzɔ siwo le ami zazã me le adrenergic stimulation te ɖo, si fia be MT-II ate ŋu akpɔ ŋusẽ ɖe dzoxɔxɔ ƒe dzɔdzɔ dzi le ami ɣi ƒe lãkusi me to veveseseɖeamenu ƒe lãmekawo ƒe dɔwɔwɔ dzi kpɔkpɔ me, si ana wòawɔ akpa aɖe le ŋusẽ ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dadasɔ me.
MT-II ate ŋu ana dzoxɔxɔ naɖiɖi le sisiblisiwo me to mast cells ƒe dɔwɔwɔ kple histamine dodo ɖe go me. Dɔwɔwɔ sia ɖe akpa si MT-II wɔna le dzoxɔxɔ dzi kpɔkpɔ ƒe mɔnuwo me fia.
Ŋusẽ si wòate ŋu akpɔ ɖe vidzidzi ƒe ɖoɖoa dzi
MT-II ate ŋu akpɔ ŋusẽ ɖe vidzidzi ƒe ɖoɖoa hã dzi. Wosrɔ̃ nu tso eŋu hena ŋutsu ƒe tsitretsitsi ƒe dɔmawɔmawɔ nyuie, si do ƒome kple ŋusẽ si wòkpɔna ɖe vidzidzi ƒe dɔwɔwɔ dzi.
Melanotan-II ƒe dɔwɔwɔ
Dɔwɔwɔ le atsyɔ̃ɖoɖodɔwɔƒewo
Le atsyɔ̃ɖoɖodɔwɔƒewo la, wozãa MT-II koŋ abe lãgbalẽwutike ene. Esi didi si le dzidzim ɖe edzi be yeƒe ŋutigbalẽ nanɔ lãmesẽ me, si le abe akɔbli ene eye wole dzi tsim ɖe nusiwo ate ŋu agblẽ le ŋutigbalẽ ŋu le ɣe ƒe keklẽ si wozãna tsã me (abe ɣe ƒe dzoxɔxɔ kple ŋutigbalẽ me kansa ƒe afɔku si le dzidzim ɖe edzi ene) ŋu ta la, amewo ƒe susu va le MT-II ŋu be enye atike si wogblɔ be ena woate ŋu awɔ ŋutigbalẽ ƒe ŋutigbalẽ ŋudɔ evɔ meɖoa ŋu ɖe ɣe ƒe keklẽ ŋu o. Gake esi wònye be dɔwɔƒe siwo ŋu ŋusẽ le abe FDA ene meda asi ɖe edzi o eye womewɔ numekuku gãwo le dedienɔnɔ kple dɔwɔwɔ ŋu o ta la, eƒe zazã le atsyɔ̃ɖoɖo ƒe asitsatsa me gakpɔtɔ le teƒe ɣi aɖe. Le dukɔ kple nuto aɖewo me la, MT-II dzadzra le Internet dzi madzemadzee hena atsyɔ̃ɖoɖo dzɔna ɣeaɖewoɣi.
Dɔwɔwɔ le Atikewɔwɔ Ŋuti Numekuku Me
Le atikewɔwɔ ŋuti numekuku gome la, MT-II zazã koŋ ku ɖe alesi wòate ŋu azãe le atikewɔwɔ me na dɔléle vovovowo me dzodzro ŋu. Le ahɔhɔ̃mekawo ƒe nuwɔna ƒe kuxiwo gome la, MT-II ɖee fia be ewɔa dɔ nyuie le ahɔhɔ̃mekawo ƒe nuwɔna ƒe tɔtrɔ siwo tso nuɖuɖu si me ami sɔ gbɔ ɖo le sɔmelãwo me kple nuwɔna ƒe gbɔdzɔgbɔdzɔ siwo le abe autism ene le MIA mice ŋutsuwo me la dodo ɖe ŋgɔ me, si na numekuku ƒe mɔfiame yeyewo le ahɔhɔ̃mekawo ƒe dɔléle siwo do ƒome kplii dada ŋu.
Le numekuku siwo wowɔ tso ŋusẽ ƒe asitɔtrɔ kple dɔléle siwo do ƒome kple dzoxɔxɔ ƒe ɖoɖowɔwɔ ŋu me la, MT-II ƒe xɔname ƒe ŋusẽkpɔɖeamedzi ɖe dzoxɔxɔ ƒe dzɔdzɔ dzi le sisiblisi siwo me PACAP mele o me ɖee fia be asixɔxɔ si ate ŋu anɔ eŋu le lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlélewo abe lolo akpa ene dada me. Numekuku bubuwo wɔwɔ le MT-II ƒe ɖoɖowɔwɔ ƒe mɔnuwo ŋu le dzesimɔ siwo do ƒome kple ŋusẽ ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu ŋu ate ŋu ana woato atike yeyewo vɛ na lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlélewo. Numekuku siwo woawɔ tso mɔnu siwo gbɔ dzoxɔxɔ si MT-II hena vɛ ŋu hã ate ŋu ana míaƒe gɔmesese nade to ɖe edzi le dzoxɔxɔ ƒe ɖoɖowɔwɔ ƒe ŋutilã me dɔwɔwɔwo ŋu, si ana nukpɔsusu ƒe gɔmeɖoanyi na dɔléle siwo do ƒome kple dzoxɔxɔ ƒe dɔmawɔmawɔ nyuie dada.
Le vidzidzi ƒe dɔlélewo gome la, numekuku siwo wowɔ tso MT-II zazã hena tsitretsitsi ƒe dɔmawɔmawɔ nyuie dada ŋu, togbɔ be egakpɔtɔ le eƒe gɔmedzedze hã la, na tiatia yeye aɖe si woatsɔ ada ŋutsuwo ƒe gbɔdɔdɔ ƒe dɔmawɔmawɔ nyuie.
Nyanuwuwuw
Melanotan-II, abe α-melanocyte-stimulating hormone analog si wowɔ ene la, ƒe nugbagbeŋusẽ ƒe dɔwɔwɔ geɖe le esi siwo dometɔ aɖewoe nye ŋutigbalẽ ƒe amadede, ahɔhɔ̃mekawo ƒe nuwɔna, ŋusẽ ƒe asitɔtrɔ, dzoxɔxɔ ƒe ɖoɖowɔwɔ, kple vidzidzi ƒe ɖoɖoa. Le ŋutigbalẽ ƒe amadede gome la, ate ŋu ana ŋutigbalẽ nado viviti, si ana mɔ aɖe si ate ŋu ana ŋutigbalẽa naɖe ɖa. Le atikewɔwɔ ŋuti numekuku gome la, MT-II ɖea mɔkpɔkpɔ siwo keke ta be woazãe fiana. Numekuku siwo wowɔ le ahɔhɔ̃mekawo ƒe nuwɔna ƒe kuxiwo, ŋusẽ ƒe asitɔtrɔ kple dɔléle siwo do ƒome kple dzoxɔxɔ ƒe dɔwɔwɔ, kple vidzidzi ƒe dɔlélewo ŋu na mɔfiame yeyewo le nɔnɔme siawo dada ŋu.
Dzɔtsoƒewo
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[2] Wekwejt P, Wojda U, Kiryk A. Melanotan-II trɔa ŋkuɖoɖonudzi ƒe gbɔdzɔgbɔdzɔ si HF nuɖuɖu ɣeyiɣi kpui aɖe hena vɛ[J]. Nu gbagbewo ƒe atikewɔwɔ & Atikewɔwɔ, 2023, 165: 115129.DOI: 10.1016 / j. biopha.2023.115129.
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[4] Gilhooley E, Daly S, McKenna D. Melanotan II Zãla ƒe Nuteƒekpɔkpɔ: Nɔnɔme Ŋuti Numekuku le Internet Dzi Numedzodzro ƒe Nyamedzroƒewo[J]. Lãmesẽŋutinunya, 2021, 237 (6): 995-999.DOI: 10.1159 / 000514492.
[5] Peters B, Hadimeri H, Wahlberg R, kple ame bubuwo. Melanotan II: nusi ate ŋu ahe ayiku ƒe ʋuʋu vɛ: agbalẽwo me toto kple dɔléle ŋuti nyatakaka[J]. Cen Nyawo ƒe Nyatakakawo, 2020, 9 (2): 159-161.DOI: 10.1007 / s13730-020-00447-z.
[6] Paiva L, Sabatier N, Leng G, kple ame bubuwo. Ŋusẽ si Melanotan-II kpɔna ɖe ahɔhɔ̃mekawo ƒe dɔlélenutsiŋutete kple Oxytocin ƒe ahɔhɔ̃mekawo ƒe dɔwɔwɔ kple eƒe dodo le lãwo me dzi[J]. Journal of ahɔhɔ̃mekawo ƒe dɔwɔwɔ, 2017,29 (2).DOI: 10.1111 / jne.12454.
Adzɔnu si li na numekuku zazã ɖeɖeko:
