Bya Cocer Peptides 
ennaku 30 eziyise
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okutwalira awamu
SS-31, era emanyiddwa nga Elamipretide, ye peptide ey’akawoowo akapya aka cationic peptide. SS-31 esobola okusala mu ddembe ekiziyiza omusaayi n’obwongo, ekintu ekigifuula esaanira okujjanjaba obuzibu bw’obusimu. Ekiziyiza omusaayi n’obwongo kikola ng’ekiziyiza ekikulu eky’obukuumi eri enkola y’obusimu ey’omu makkati, ng’eddagala erisinga lilwana okugisala. Kyokka, SS-31 evvuunuka obuzibu buno, n’etuuka butereevu mu kifo awaali okwonooneka kw’obusimu era n’ewa essuubi ery’okuddaabiriza okwonooneka kw’obutoffaali bw’obusimu. Kibeera mu kiraasi ya peptides eza molekyu entono, nga zirina obuzito bwa molekyu obutono, ekigiwa okutambula okulungi n’okubeera n’ebiramu mu mubiri. Cations ezisitulibwa SS-31 zigisobozesa okukwatagana n’ebitundu ebirina omusannyalazo omubi eby’obuwuka obuyitibwa biological membranes naddala phospholipids z’oluwuzi olw’omunda olulina omusannyalazo omubi (negative charged phospholipids) eza mitochondria. Okusiba kuno okwetongodde kusobozesa SS-31 okukuŋŋaanyizibwa mu mitochondria, bwe kityo n’ekola ebikolwa byayo eby’okulungamya ku nkola ya mitochondria.
Ekifaananyi 1 Enkola y’okukola kwa SS-31 ku bulwadde bw’ekibumba.
Enkola y’Ekikolwa
Okulungamya Enkola ya Mitochondrial
Mitochondria, nga amaanyi g’obutoffaali, zikola kinene nnyo mu bulamu bw’obutoffaali n’okukyusakyusa mu mubiri. SS-31, n’ensengekera yaayo eya cationic, esobola okukuŋŋaanyizibwa ennyo mu phospholipids z’oluwuzi olw’omunda ezirina omusannyalazo omubi eza mitochondria, bwe kityo n’eyongera ku kussa kwa mitochondria. Olujegere lw’okussa olwa mitochondrial kkubo ddene nnyo mu kukola amaanyi g’obutoffaali (ATP). SS-31 elongoosa enkola ya puloteyina ezikwatagana mu lujegere lw’okussa, n’elongoosa obulungi bw’entambula y’obusannyalazo, bwe kityo n’etumbula okusengejja kwa ATP n’okuwa obutoffaali amaanyi agamala okukuuma emirimu gy’omubiri egya bulijjo ng’okugabanya obutoffaali, okwawukana, n’okutambuza ebintu.
SS-31 ekola enkola y’obutonde bw’omubiri (mitochondrial biogenesis) mu busimu obuyitibwa neurons, n’etumbula okuzaala kwa mitochondria empya. Obutoffaali bwe boolekagana n’okwonooneka oba okunyigirizibwa, okutondebwa kwa mitochondria empya kuyamba okujjuza mitochondria ezonoonese oba ezitakola bulungi, okukuuma obulamu bw’ekibinja kya mitochondria munda mu katoffaali. Era kyongera ku mitochondrial autophagy, enkola y’obutoffaali ey’okugogola mitochondria eyonoonese. Singa mitochondria eyonoonese tezilongoosebwa mangu, zifulumya ebika bya oxygen ebikola (ROS), ne byongera okwonoona obutoffaali. SS-31 ekendeeza bulungi ku kukola ROS nga eyongera ku mitochondrial autophagy, bwe kityo n’ekuuma obutoffaali okuva ku kwonooneka kwa oxidative stress.
Okuziyiza okuddamu kw’okuzimba
Mu nkola nnyingi ez’okwonooneka kw’obutoffaali, okuddamu kw’okuzimba kutera okuwerekera okwonooneka. Cytoplasmic phospholipase A2 (cPLA2), nga omutabaganya omukulu ow’okuzimba obusimu, emenya phospholipids z’olususu ku kifo kya sn-2 ekya lysosomes wansi w’embeera z’obulwadde, n’ekola lysophospholipids ne ω3 polyunsaturated fatty acids, ekivaako lysosomal membrane permeabilization (LMP) n’okutondawo embeera y’okuzimba. SS-31 esobola okukendeeza ku ddaala ly’okwolesebwa kwa phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), okuziyiza phosphorylation ya cPLA2, bwe kityo n’ekendeeza ku kukola kw’abatabaganya okuzimba n’okukendeeza ku kwonooneka okuva mu kuddamu kw’okuzimba eri obutoffaali.
Mu kunoonyereza ku buvune bw’emisuwa gy’omutima obuva ku sepsis, SS-31 yazuulibwa nti eziyiza okukola kwa NF-κB ne NLRP3, bwe kityo n’elongoosa okuddamu kw’okuzimba kw’emisuwa gy’omutima. NF-κB ye regulator enkulu ey’amakubo g’obubonero bw’okuzimba, ate NLRP3 kitundu kikulu nnyo mu inflammasome. Okukola kwazo kuleeta okufulumya omuwendo omunene ogw’ebintu ebizimba, nga IL-6, IL-1β, ne TNF-α. Nga eziyiza okukola kw’ensonga zino ebbiri enkulu, SS-31 ekendeeza ku miwendo gy’okwolesebwa kw’ensonga ezizimba, ekendeeza ku kwonooneka kw’okuzimba obutoffaali bw’emisuwa gy’omutima, n’okukuuma emirimu gyabwo egya bulijjo.
Okutumbula autophagy n’okuziyiza pyroptosis
Autophagy nkola nkulu ey’okwekuuma mu butoffaali egogola ebitundu by’omubiri ebyonooneddwa, puloteyina ezibikkiddwa obubi, n’ebintu ebirala eby’obulabe. Mu kunoonyereza ku buvune bw’omugongo, kyazuulibwa nti SS-31 eyongera ku miwendo gya puloteyina ezikwatagana n’okulya nga Beclin-1, VPS34, ne LC3, ekendeeza ku miwendo gya puloteyina ezikwata ku autophagy substrate nga p62, naye tekosa miwendo gya puloteyina ezikwatagana n’obutonde bw’omubiri (lysosomal biogenesis-related proteins) nga ATP6V1B2 ne LAMP1. Kino kiraga nti SS-31 esobola okukwata ku kutondebwa kwa autophagosomes oluvannyuma lw’okulumwa omugongo, nga p62, awatali kukosa miwendo gya puloteyina ezikwatagana n’obutonde bw’omubiri (lysosomal biogenesis-related proteins), nga ATP6V1B2 ne LAMP1. Kino kiraga nti SS-31 esobola okufuga okutondebwa kwa autophagosomes oluvannyuma lw’okulumwa omugongo, okutumbula enkulaakulana eya bulijjo ey’ekkubo lya autophagy, okuyamba obutoffaali mu kugogola ebitundu ebyonooneddwa, n’okuzzaawo obutebenkevu bw’embeera y’omu butoffaali.
Pyroptosis ye inflammatory programmed necrosis ekivaako okwonooneka kw’obutoffaali okuyitiridde mu ndwadde ez’enjawulo. SS-31 ekendeeza ku miwendo gya puloteyina ezikwatagana ne pyroptosis, nga ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, ne IL-18, bwe kityo ne kiziyiza okubeerawo kwa pyroptosis. Waliwo enkolagana enzibu wakati wa autophagy ne pyroptosis; okutumbula autophagy kiyinza okuziyiza pyroptosis. SS-31 etereeza bbalansi eno, ekendeeza bulungi okufa kw’obutoffaali okuva ku pyroptosis n’okutumbula okuddaabiriza n’okuwangaala kw’obutoffaali.
Okusaba
Endwadde z’obusimu
Obuvune bw’omugongo mbeera ya maanyi erema ekivaako okufiirwa emirimu egy’olubeerera n’okukosa enkola y’emirimu. Olw’okuba nti waliwo ekiziyiza omusaayi n’obwongo, eddagala erya bulijjo lilwana okutuuka mu kifo ekifunye obuvune. SS-31, n’obusobozi bwayo okusala ekiziyiza omusaayi n’obwongo, eraga obusobozi obusuubiza mu kujjanjaba obuvune bw’omugongo. Bwe yaweebwa nga bayita mu mpiso mu lubuto ku mbeba ezirina obuvune ku mugongo, okwekenneenya enneeyisa nga tukozesa minzaani y’ebibe eya BMS, okwekenneenya entambula, n’okukebera ennyonyi eziserengese byalaga nti kitumbula nnyo okudda engulu mu nkola oluvannyuma lw’obuvune. Mu by’obutonde, nga tukozesa HE, Masson, MAP2, ne SYN staining, kyazuulibwa nti SS-31 ekendeeza ku kitundu ky’enkovu z’omugongo, eyongera ku muwendo gwa dendrites ne synapses, era etumbula okuddaabiriza enzimba n’enkola y’obusimu bw’omugongo.
Mu kunoonyereza ku ndwadde ezimu ezikendeeza ku busimu, gamba ng’obulwadde bwa Parkinson n’obulwadde bwa Alzheimer, SS-31 nayo eraga omugaso oguyinza okujjanjaba. Endwadde zino zitera okuwerekerwako okwonooneka kw’obusimu obuyitibwa oxidative stress-induced neuronal damage, inflammatory responses, n’obutakola bulungi bwa mitochondrial. SS-31, okuyita mu nkola eziwera nga okulungamya enkola ya mitochondria, okuziyiza okuddamu kw’okuzimba, n’okutumbula autophagy y’obutoffaali, erina ekisuubizo eky’okulwawo okuvunda kw’obusimu n’okulongoosa obubonero bw’omulwadde.
Endwadde z’emisuwa n’emisuwa
Omutima obutakola bulungi kizibu kya bulijjo era ekiyinza okutta omuntu olw’obulwadde bwa sepsis. SS-31 eraga ebikolwa eby’obukuumi ku buvune bw’emisuwa gy’omutima mu sepsis. Mu kugezesa mu vivo, ebibe mu kibinja ky’okuyingira mu nsonga za SS-31 byalaga okulongooka ennyo mu butategeka ebitundu by’emisuwa gy’omutima n’okuyingira mu kuzimba bw’ogeraageranya n’ekibinja kya sepsis, n’okukendeera okw’amaanyi mu butoffaali obufa. SS-31 esobola okuziyiza upregulation y’ensonga okuzimba mu myocardial tissue, okwongera ATP content, okulongoosa redox status, okukuuma mitochondrial membrane potential, n’okuziyiza activation ya NF-κBp65 ne NLRP3, bwe kityo okukendeeza LPS-induced myocardial obuvune. Kino kiraga nti SS-31 eyinza okufuuka eddagala eriyinza okujjanjaba obulwadde bw’omutima obuva ku sepsis.
Mu ndwadde endala ez’emisuwa, gamba ng’obuvune mu myocardial ischemia-reperfusion, SS-31 nayo eyinza okukola kinene. Enkola ya myocardial ischemia-reperfusion ereeta okukola omuwendo omunene ogwa ROS, ekivaako okuddamu kw’okuzimba n’okufa kw’obutoffaali.
Mu bufunzi
SS-31 esobola okuyingira mu kiziyiza omusaayi n’obwongo, okutuuka ku mitochondria okuddaabiriza okwonooneka kw’obutoffaali, era esobola okukozesebwa mu ndwadde z’obusimu, endwadde z’emisuwa, okuddaabiriza ebinywa by’amagumba, n’obuvune bw’emisuwa gya ssukaali. Nga etunuulira mitochondria nga ekigendererwa ekikulu, kiwa endowooza empya ey’obujjanjabi.
Ensonda
[1] Zhu Y, Luo M, Bai X, n’abalala. SS-31, Peptide egenderera Mitochondria, Etereeza Obulwadde bw’Ekibumba[J]. Eddagala ly’omukka n’obulamu obuwanvu bw’obutoffaali, 2022,2022:1295509.DOI:10.1155/2022/1295509.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
