By Cocer Peptides 
1 ọnwa 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 nke PE22-28
PE22-28 bụ peptide 7-amino acid emebere dabere na nyocha n'ime Spadin (PE 12-28). A na-emeso ịda mbà n'obi, nsogbu uche nke na-emetụta ihe dịka 20% nke ọnụ ọgụgụ ụwa, ugbu a na antidepressants nke na-ata ahụhụ site na nsogbu ndị dị ka ịmalite ime ihe na-egbu oge na mmetụta ọjọọ. A kọwara Spadin dị ka peptide endogenous nwere ọrụ antidepressant nke na-egbochi ọwa TREK-1, mana ọrụ ya na-apụ n'anya n'ime awa 7 mgbe nchịkwa gasịrị. Iji kwalite nkwụsi ike nke Spadin na bioavailability na vivo, ndị nchọpụta nyochara ihe analogs na ihe ndị ọzọ, na-amụ ngwaahịa mmebi ọbara nke Spadin, ma mechaa mepụta PE22-28.
Ọgụgụ 1 Spadin-analog nkọwa. (A-D) PE 22-28 ejiri mee ihe dị ka peptide nnọchiteanya maka ịnwale nkọwa nke spadin-analogs vs. K2P channels ndị ọzọ, TREK-2 (A), TRAAK (B), TRESK (C), na TASK-1 (D).
Ọrụ nke PE22-28
Mmetụta na ọwa TREK-1
Ọmụmụ ihe ọmụmụ vitro na-eji teknụzụ patch-clamp na sel hTREK-1 / HEK gosipụtara na PE22-28 gosipụtara nkọwapụta kachasị mma na mmekọrịta maka ọwa TREK-1 ma e jiri ya tụnyere Spadin. Data akọwapụtara na-egosi na IC₅₀ nke PE22-28 bụ 0.12 nM, ebe nke Spadin bụ 40-60 nM. Nke a pụtara na n'okpuru otu ọnọdụ, PE22-28 nwere ike na-arụ ọrụ na TREK-1 ọwa nke ọma na obere mkpokọta, si otú na-arụ ọrụ ya ndu mmetụta kpọmkwem. Ọmụmụ ihe ahụ kwukwara na n'okpuru otu ọnọdụ ahụ, mgbanwe dị iche iche na N- ma ọ bụ C-terminus nke PE22-28 nwere ike ịnọgide na-enwe ma ọ bụ kpochapụ ọrụ TREK-1 na-enweghị emetụta mmekọrịta ya maka ọwa TREK-1. Usoro nhazi a pụrụ iche nke ọrụ ọwa na mmekọrịta ya na-enye ihe ngosi dị mkpa maka nyocha ọzọ n'ime usoro ọrụ ya na mmepe ọgwụ.
Mmetụta antidepressant na vivo
Nkwenye ụdị omume: N'ụdị omume ịda mbà n'obi dị ka ule igwu mmiri amanye, akwadoro ihe ndị na-egbochi ịda mbà n'obi nke PE22-28 na ihe ndị na-emepụta ya. Ụmụ oke ejiri Spadin analogues emeso ya (gụnyere PE22-28) gosipụtara mbelata dị ukwuu na oge enweghị ike imeghari. Oge nkwụsịtụ bụ ihe dị mkpa na-egosi omume ịda mbà n'obi-dị ka ụmụ oke n'oge ule igwu mmiri na-amanye, na mbelata oge nkwụsịtụ na-egosi mbelata nke omume ịda mbà n'obi, na-atụ aro na PE22-28 nwere mmetụta antidepressant. N'ime ule nri amachibidoro nke ọhụrụ ka ụbọchị anọ nke ọgwụgwọ subchronic gasịrị, PE22-28 belatara nke ukwuu oge nkwụsị nke ụmụ oke iji rie pellet nri. Nnwale nri egbochiri nke ọhụrụ bụ usoro nnwale iji chọpụta njikere ụmụ oke nwere iri nri na gburugburu ebe ọhụrụ. Oge nkwụsịtụ dị mkpụmkpụ na-egosi mbelata nchekasị na omume ịda mbà n'obi na ụmụ oke, na-akwadokwa mmetụta antidepressant nke PE22-28.
Mmetụta na neurogenesis na synaptogenesis: Mgbe naanị 4 ụbọchị ọgwụgwọ, PE22-28 na analogues ya kpatara neurogenesis, na G / A-PE22-28 na-egosi mmetụta dị ịrịba ama. Neurogenesis na-arụ ọrụ dị mkpa na pathogenesis nke ịda mbà n'obi na nzaghachi ọgwụgwọ, na ọgbọ nke neurons ọhụrụ na-enyere aka melite ọrụ akwara na ọnọdụ ọnọdụ. N'ime neurons cortical mouse, PE22-28 na ihe ndị sitere na ya kwalitekwara synaptogenesis, dị ka atụpụtara site na mmụba okwu PSD-95. PSD-95 bụ protein jikọtara ya na mpaghara postsynaptik, yana mmụba ọkwa ọkwa na-egosi nhazi synapse na arụ ọrụ, na-eme ka mgbasa ozi dị n'etiti neurons na nhazigharị sekit neural, nke dị oke mkpa maka ịkwalite mgbaàmà ịda mbà n'obi.
Uru na oge nke ime ihe: E jiri ya tụnyere Spadin, ogologo oge nke PE22-28 na analogues na-eme ka ọ dịkwuo mma. Spadin na-efunahụ ọrụ ya 7 awa mgbe nchịkwa gasịrị, ebe oge ọrụ nke PE22-28 nwere ike iru ruo awa 23. Ogologo oge nke ime ihe pụtara na mmetụta ya nwere ike ịdịgide ogologo oge na vivo, na-ebelata oge nchịkwa na imeziwanye nnabata onye ọrịa, nke nwere mmetụta dị mkpa maka ọgwụgwọ ụlọ ọgwụ.
Ngwa nke PE22-28
Ngwa nwere ike ime na ọgwụgwọ ịda mbà n'obi: N'inyere PE22-28 dị mma nke ọma na ụdị omume antidepressant, usoro ya pụrụ iche na-eme na ọwa TREK-1, na mmetụta ya dị mma na neurogenesis na synaptogenesis, ọ na-anọchite anya molekul na-ekwe nkwa nke nwere ike dochie Spadin na ọgwụgwọ ịda mbà n'obi. Mpụta nke PE22-28 na-enye nhọrọ ọgwụgwọ ọhụrụ maka ịda mbà n'obi. Ọ ghọwo ntụziaka dị mkpa maka mmepe nke ọgbọ ọzọ nke ọgwụ antidepressant. Site na nyocha na mmepe n'ihu, na-eme ka usoro ọgwụ ya na usoro nchịkwa ya dịkwuo mma, a na-atụ anya na ọ ga-enye nhọrọ ọgwụgwọ dị irè maka ndị ọrịa nwere ịda mbà n'obi.
Isi mmalite
[1] Djillani A, Pietri M, Moreno S, et al. Analogs Spadin Shortened Na-egosiputa Mmachi TREK-1, Na Vivo Stability na Antidepressant Arụ Ọrụ[J]. Ihu ihu na Pharmacology, 2017,8:643.DOI:10.3389/fphar.2017.00643.
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