Los ntawm Cocer Peptides 
1 month ago
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam ntawm PE22-28
PE22–28 yog 7-amino acid peptide tsim los ntawm kev tshawb fawb hauv Spadin (PE 12–28). Kev nyuaj siab, kev puas siab puas ntsws cuam tshuam txog kwv yees li 20% ntawm cov pej xeem hauv ntiaj teb, tam sim no tau kho nrog cov tshuaj tiv thaiv kev nyuaj siab uas raug kev txom nyem los ntawm cov teeb meem xws li kev ncua sij hawm ua haujlwm thiab cov kev mob tshwm sim hnyav. Spadin tau piav qhia tias yog endogenous peptide nrog cov tshuaj tiv thaiv kev ntxhov siab uas tshwj xeeb thaiv TREK-1 channel, tab sis nws cov haujlwm ploj hauv 7 teev tom qab tswj hwm. Txhawm rau txhim kho Spadin qhov ruaj khov thiab bioavailability hauv vivo, cov kws tshawb fawb tau tshuaj xyuas nws cov analogs thiab cov khoom siv, kawm Spadin cov khoom degradation ntshav, thiab thaum kawg tsim PE22-28.
Daim duab 1 Spadin-analog tshwj xeeb. (A–D) PE 22-28 tau siv los ua tus sawv cev peptide rau kev sim qhov tshwj xeeb ntawm spadin-analogs vs.
Kev ua haujlwm ntawm PE22-28
Qhov cuam tshuam rau TREK-1 Channels
Cov kev tshawb fawb hauv vitro siv lub tshuab patch-clamp ntawm hTREK-1 / HEK hlwb tau pom tias PE22-28 nthuav tawm qhov tshwj xeeb zoo dua thiab kev sib raug zoo rau TREK-1 raws piv rau Spadin. Cov ntaub ntawv tshwj xeeb qhia tau tias IC₅₀ ntawm PE22-28 yog 0.12 nM, thaum Spadin yog 40-60 nM. Qhov no txhais tau hais tias nyob rau hauv tib lub sijhawm, PE22-28 tuaj yeem ua rau TREK-1 channel zoo dua ntawm qhov qis dua, yog li ua rau nws cov teebmeem lom neeg ntau dua. Txoj kev tshawb no kuj tau sau tseg tias nyob rau hauv tib lub sijhawm, kev hloov pauv sib txawv ntawm N- lossis C-qhov kawg ntawm PE22-28 tuaj yeem tswj lossis tshem tawm TREK-1 channel yam tsis muaj kev cuam tshuam rau nws txoj kev sib raug zoo rau TREK-1 channel. Qhov kev tswj hwm tshwj xeeb ntawm kev ua haujlwm channel thiab kev sib raug zoo muab cov ntsiab lus tseem ceeb rau kev tshawb fawb ntxiv rau hauv nws cov txheej txheem ntawm kev ua thiab kev tsim tshuaj.
Antidepressant teebmeem hauv vivo
Kev coj tus cwj pwm validation: Hauv cov qauv kev nyuaj siab xws li kev sim ua luam dej, cov tshuaj tiv thaiv kev nyuaj siab ntawm PE22-28 thiab nws cov txiaj ntsig tau lees paub. Cov nas kho nrog Spadin analogues (xws li PE22-28) pom qhov txo qis hauv lub sijhawm tsis muaj zog. Lub sij hawm Immobilization yog ib qho tseem ceeb qhia txog kev nyuaj siab zoo li tus cwj pwm hauv cov nas thaum lub sij hawm yuam kev ua luam dej, thiab kev txo qis hauv lub sij hawm immobilization qhia tau hais tias tus cwj pwm zoo li kev nyuaj siab txo qis, qhia tias PE22-28 muaj cov tshuaj tiv thaiv kev nyuaj siab. Hauv kev sim pub mis tshiab tshiab tom qab 4 hnub ntawm kev kho mob subchronic, PE22-28 txo qis lub sijhawm latency rau cov nas noj cov zaub mov pellets. Qhov kev ntsuam xyuas kev noj zaub mov tshiab uas txwv tsis pub noj yog ib txoj hauv kev sim los ntsuas cov nas txaus siab noj hauv ib puag ncig tshiab. Lub sijhawm luv latency qhia tau hais tias txo kev ntxhov siab thiab kev nyuaj siab txog tus cwj pwm hauv cov nas, ntxiv kev lees paub txog cov tshuaj tiv thaiv kev nyuaj siab ntawm PE22-28.
Cov teebmeem ntawm neurogenesis thiab synaptogenesis: Tom qab 4 hnub ntawm kev kho mob, PE22-28 thiab nws cov analogues induced neurogenesis, nrog G / A-PE22-28 qhia txog cov teebmeem tshwj xeeb. Neurogenesis plays lub luag haujlwm tseem ceeb hauv cov kab mob ntawm kev nyuaj siab thiab kev kho mob, thiab tsim cov neurons tshiab pab txhim kho neural muaj nuj nqi thiab lub siab lub ntsws. Hauv nas cortical neurons, PE22-28 thiab nws cov derivatives kuj tau txhim kho synaptogenesis, raws li ntsuas los ntawm nce qib PSD-95 qhia. PSD-95 is a protein associated with the postsynaptic dense region, and increased expression levels indicate enhanced synapse formation and function, facilitating information transmission between neurons and neural circuit remodeling, which is of significant importance for improving depressive symptoms.
Qhov zoo ntawm lub sijhawm ua haujlwm: Piv rau Spadin, lub sijhawm ua haujlwm ntawm PE22-28 thiab nws cov analogues tau zoo dua qub. Spadin poob nws cov haujlwm 7 teev tom qab kev tswj hwm, thaum lub sijhawm ua haujlwm ntawm PE22-28 tuaj yeem ncav cuag 23 teev. Lub sijhawm ntev ntawm kev ua haujlwm txhais tau hais tias nws cov teebmeem lom neeg tuaj yeem txhawb nqa lub sijhawm ntev hauv vivo, txo qhov zaus ntawm kev tswj hwm thiab txhim kho kev ua raws li tus neeg mob, uas muaj qhov cuam tshuam tseem ceeb rau kev kho mob.
Kev siv ntawm PE22-28
Muaj peev xwm siv tau hauv kev kho kev nyuaj siab: Muab PE22-28 qhov ua tau zoo hauv cov qauv kev tiv thaiv kev ntxhov siab, nws cov txheej txheem tshwj xeeb ntawm kev ua haujlwm ntawm TREK-1 channel, thiab nws cov txiaj ntsig zoo ntawm neurogenesis thiab synaptogenesis, nws sawv cev rau kev cog lus molecule nrog lub peev xwm los hloov Spadin hauv kev kho kev nyuaj siab. Qhov tshwm sim ntawm PE22-28 muaj kev kho mob tshiab rau kev nyuaj siab. Nws tau dhau los ua ib qho kev taw qhia tseem ceeb rau kev txhim kho cov tiam tom ntej ntawm cov tshuaj tiv thaiv kev ntxhov siab. Los ntawm kev tshawb fawb thiab kev txhim kho ntxiv, ua kom zoo dua nws cov tshuaj tsim thiab kev tswj hwm, nws xav tias yuav muab kev kho mob zoo dua rau cov neeg mob kev nyuaj siab.
Qhov chaw
[1] Djillani A, Pietri M, Moreno S, et al. Shortened Spadin Analogs Pom Zoo TREK-1 Inhibition, Hauv Vivo Stability thiab Antidepressant Activity [J]. Frontiers in Pharmacology, 2017,8:643.DOI:10.3389/fphar.2017.00643.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
