Site na Cocer Peptides 
ụbọchị 30 gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
SS-31, nke a makwaara dị ka Elamipretide, bụ peptide cationic na-esi ísì ụtọ. SS-31 nwere ike ịfefe ihe mgbochi ụbụrụ nke ọbara, ihe onwunwe nke na-eme ka ọ dị mma maka ọgwụgwọ ọrịa akwara ozi. Ihe mgbochi ụbụrụ nke ọbara na-eje ozi dị ka ihe mgbochi dị oke mkpa maka sistemu ụjọ nke etiti, yana ọtụtụ ọgwụ na-agbasi mbọ ike ịgafe ya. Otú ọ dị, SS-31 meriri mmachi a, na-eru kpọmkwem ebe mmebi akwara ma na-enye olileanya maka ịrụzi mmebi nke mkpụrụ ndụ akwara. Ọ bụ klaasị nke peptides pere mpe, nke nwere ịdị arọ molekụla dị obere, nke na-enye ya ezigbo ngagharị na bioavailability n'ime ahụ. cations nke SS-31 na-ebu na-enyere ya aka imekọrịta ihe na-adịghị mma nke membranes ndu, ọkachasị akpụkpọ ahụ dị n'ime phospholipids nke mitochondria na-adịghị mma. Njikọ a kpọmkwem na-enye SS-31 ohere ịgbakọta na mitochondria, si otú ahụ na-arụ ọrụ nchịkwa ya na ọrụ mitochondrial.
Ọgụgụ 1 Usoro ọrụ nke SS-31 megide ọrịa akụrụ.
Usoro nke Omume
Iwu nke ọrụ Mitochondrial
Mitochondria, dị ka ụlọ ike nke cell, na-arụ ọrụ dị mkpa na ndụ cellular na metabolism. SS-31, ya na usoro cationic ya, nwere ike ịgbakọ n'ọtụtụ ebe na akpụkpọ anụ phospholipids dị n'ime nke mitochondria na-adịghị mma, si otú a na-eme ka iku ume mitochondrial dịkwuo elu. Igwe iku ume mitochondrial bụ ụzọ dị oke mkpa maka mmepụta ike cell (ATP). SS-31 na-ebuli ọrụ nke protein ndị metụtara ya na agbụ iku ume, na-emeziwanye arụmọrụ njem elektrọn, si otú a na-akwalite njikọ ATP ma na-enye mkpụrụ ndụ ike zuru oke iji nọgide na-eme ihe omume physiological nkịtị dị ka nkewa cell, ọdịiche, na njem ihe.
SS-31 na-arụ ọrụ biogenesis mitochondrial na neurons, na-akwalite ọgbọ nke mitochondria ọhụrụ. Mgbe mkpụrụ ndụ na-eche mmebi ma ọ bụ nrụgide ihu, ọgbọ nke mitochondria ọhụrụ na-enyere aka mejupụta mitochondria mebiri emebi ma ọ bụ na-adịghị arụ ọrụ, na-edobe ahụike nke mitochondrial bi n'ime cell. Ọ na-akwalitekwa mitochondrial autophagy, usoro cellular maka ikpochapụ mitochondria mebiri emebi. Ọ bụrụ na ewepụghị mitochondria mebiri emebi ngwa ngwa, ha na-ahapụ nnukwu ụdị oxygen na-emeghachi omume (ROS), mkpụrụ ndụ na-emebi emebi. SS-31 na-ebelata mmepụta ROS nke ọma site n'ịkwalite autophagy mitochondrial, si otú ahụ na-echebe mkpụrụ ndụ site na mmebi nrụgide oxidative.
Na-egbochi nzaghachi mkpali
N'ọtụtụ usoro mmebi cellular, nzaghachi mkpali na-esokarị mmebi ahụ. Cytoplasmic phospholipase A2 (cPLA2), dị ka onye mgbasa ozi bụ isi nke neuroinflammation, na-agbaji akpụkpọ ahụ phospholipids na sn-2 ọnọdụ nke lysosomes n'okpuru ọnọdụ pathological, na-emepụta lysophospholipids na ω3 polyunsaturated fatty acids, na-eduga na lysosomal membrane permem. SS-31 nwere ike belata ọkwa nkwupụta nke phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), na-egbochi phosphorylation nke cPLA2, si otú ahụ belata mmepụta nke ndị mgbasa ozi na-egbuke egbuke ma na-ebelata mmebi nke nzaghachi mkpali na-akpata na sel.
N'ọmụmụ ihe gbasara mmerụ ahụ myocardial kpatara sepsis, SS-31 chọpụtara na ọ na-egbochi ọrụ NF-κB na NLRP3, si otú ahụ na-eme ka nzaghachi myocardial na-egbuke egbuke. NF-κB bụ isi nchịkwa nke ụzọ mgbaàmà mkpali, ebe NLRP3 bụ akụkụ dị mkpa nke ihe na-egbuke egbuke. Nkwalite ha na-eduga na ntọhapụ nke ọnụ ọgụgụ buru ibu nke ihe ndị na-akpata mkparị, dị ka IL-6, IL-1β, na TNF-α. Site n'igbochi ntinye nke isi ihe abụọ a, SS-31 na-ebelata ọkwa nkwupụta nke ihe ndị na-egbuke egbuke, na-ebelata mkpali mmebi nke mkpụrụ ndụ myocardial, ma nọgide na-arụ ọrụ ha.
Na-akwalite autophagy na igbochi pyroptosis
Autophagy bụ usoro dị mkpa nke na-echebe onwe ya n'ime sel nke na-ekpochapụ akụkụ ahụ ndị mebiri emebi, protein ndị gbajiri agbagọ, na ihe ndị ọzọ na-emerụ ahụ. N'ime ọmụmụ banyere mmerụ ahụ ọkpụkpụ azụ, a chọpụtara na SS-31 na-eme ka ọkwa nke protein ndị metụtara autophagy dị ka Beclin-1, VPS34, na LC3, na-ebelata ọkwa nke protein substrate autophagy dị ka p62, ma ọ dịghị emetụta ọkwa nke protein ndị metụtara lysosomal biogenesis dị ka ATP6V1B2 na LAMP1. Nke a na-egosi na SS-31 nwere ike imetụta nguzobe nke autophagosomes mgbe ọnyá azụ azụ, dị ka p62, na-enweghị emetụta ọkwa nke protein ndị metụtara lysosomal biogenesis, dị ka ATP6V1B2 na LAMP1. Nke a na-egosi na SS-31 nwere ike imetụta nguzobe nke autophagosomes mgbe ọnyá azụ azụ gasịrị, kwalite ọganihu nkịtị nke ụzọ autophagy, nyere sel aka ikpochapụ ihe ndị mebiri emebi, ma weghachite nkwụsi ike nke gburugburu intracellular.
Pyroptosis bụ necrosis nke a na-emepụta na-egbu egbu nke na-eduga n'imebi oke cellular na ọrịa dị iche iche. SS-31 na-ebelata ọkwa nke protein ndị metụtara pyroptosis, dị ka ASC, GSDMD, Caspase-1, NLRP3, NLRP1, IL-1β, na IL-18, si otú a na-egbochi ihe omume pyroptosis. Enwere mgbagwoju anya n'etiti autophagy na pyroptosis; ịkwalite autophagy nwere ike igbochi pyroptosis. SS-31 na-achịkwa nguzozi a, na-ebelata nke ọma ọnwụ cell nke pyroptosis kpatara na ịkwalite nrụzi cellular na nlanarị.
Ngwa
Ọrịa Neurological
Ọkpụkpụ azụ azụ bụ ọnọdụ nkwarụ siri ike na-eduga na mfu arụ ọrụ na-adịgide adịgide yana mmebi moto. N'ihi ọnụnọ nke mgbochi ụbụrụ ọbara, ọgwụ ndị a na-emekarị na-agbasi mbọ ike iru ebe ahụ merụrụ ahụ. SS-31, na ikike ya ịgafe ihe mgbochi ụbụrụ-ọbara, na-egosi ikike na-ekwe nkwa na ọgwụgwọ nke ọkpụkpụ azụ. Mgbe a na-enye ya site na intraperitoneal injections na ụmụ oke nwere mmerụ azụ azụ, nyocha omume site na iji ọnụ ọgụgụ òké BMS, nyocha gait, na nyocha ụgbọ elu na-egosi na ọ na-akwalite mgbake na-arụ ọrụ mgbe mmerụ ahụ gasịrị. N'ihe gbasara akụkọ ihe mere eme, iji HE, Masson, MAP2, na SYN staining, e kpebisiri ike na SS-31 na-ebelata ebe ọkpụkpụ azụ glial scarring, na-eme ka ọnụ ọgụgụ dendrites na synapses dịkwuo elu, ma na-akwalite nhazi nhazi na arụ ọrụ nke akwara ọkpụkpụ azụ.
N'ime nchọpụta nke ụfọdụ ọrịa neurodegenerative, dị ka ọrịa Parkinson na ọrịa Alzheimer, SS-31 egosiwokwa uru ọgwụgwọ nwere ike. Ọrịa ndị a na-esonyere ya na nrụgide oxidative na-akpata mmebi neuronal, nzaghachi mkpali, na arụrụ ọrụ mitochondrial. SS-31, site n'ọtụtụ usoro dị ka ịhazi ọrụ mitochondrial, na-egbochi nzaghachi mkpali, na ịkwalite autophagy cell, na-ekwe nkwa maka igbu oge nkwụsị nke neuronal na imeziwanye mgbaàmà ndị ọrịa.
Ọrịa obi
Mgbagwoju anya nke obi bụ ihe mgbagwoju anya na-eyi ndụ egwu nke sepsis. SS-31 na-egosipụta mmetụta nchebe megide mmerụ ahụ myocardial na sepsis. N'ime nyocha nke vivo, ụmụ oke na ndị otu ntinye aka SS-31 gosipụtara ngbanwe nke ọma na nhazigharị anụ ahụ myocardial na mkpali na-egbu egbu ma e jiri ya tụnyere otu sepsis, yana mbelata dị ukwuu na sel apoptotic. SS-31 nwere ike igbochi nkwụsị nke ihe ndị na-egbuke egbuke na anụ ahụ myocardial, na-amụba ọdịnaya ATP, meziwanye ọnọdụ redox, na-eme ka akpụkpọ anụ mitochondrial nwee ike, ma gbochie NF-κBp65 na NLRP3, si otú ahụ na-ebelata mmerụ ahụ myocardial nke LPS kpatara. Nke a na-egosi na SS-31 nwere ike ịghọ ọgwụ nwere ike ịgwọ ọrịa cardiomyopathy kpatara sepsis.
Na ọrịa obi ndị ọzọ, dị ka myocardial ischemia-reperfusion mmerụ, SS-31 nwekwara ike ịrụ ọrụ dị mkpa. Usoro myocardial ischemia-reperfusion na-eduga na mmepụta nke nnukwu ROS, na-ebute nzaghachi mkpali na cell apoptosis.
Mmechi
SS-31 nwere ike banye n'ime ihe mgbochi ụbụrụ nke ọbara, lekwasịrị anya mitochondria iji rụkwaa mmebi cellular, ma nwee ike itinye aka na ọrịa akwara ozi, ọrịa obi, nrụzi akwara skeletal, na mmerụ ahụ vaskụla endothelial ọrịa shuga. Site n'ichekwa mitochondria dị ka isi ebumnuche, ọ na-enye echiche ọgwụgwọ ọhụrụ.
Isi mmalite
[1] Zhu Y, Luo M, Bai X, et al. SS-31, Mitochondria-Targeting Peptide, Ameliorates Kidney Disease[J]. Ọgwụ Oxidative na Ogologo Ogologo Cellular, 2022,2022:1295509.DOI:10.1155/2022/1295509.
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