Na Cocer Peptides bin rayt am 
1 mɔnt dɔn pas
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ PE22–28
PE22–28 na 7-amino asid pεptida we dεn disayn bays pan risεch pan Spadin (PE 12–28). Pwɛl hat, na wan mɛntɛl disɔda wae de afɛkt lɛk 20% pan di pipul dɛm na di wɔl, naw dɛn de trit am wit antidipreshan wae de sɔfa wit tin dɛm lɛk wae de te fɔ bigin akshɔn ɛn wae kin gɛt siriɔs sayd ɛfɛkt. dεn dεskrεb spadin as εndojεnik pεptida wit antidipreshכn aktiviti we spεshal wan de blכk di TREK-1 chεnal, bכt in aktiviti de disappear insay 7 awa afta dεn gi am. fכ mek Spadin in stεbiliti εn bayoavaylabl in vivo, risechכr dεm skrεn in analכg dεm εn dεrivεt dεm, stכdi Spadin in blכd dεgradashכn prodakt dεm, εn las las dεn disayn PE22-28.
Fig 1 Spadin-analog spɛsifisiti. (A–D) PE 22-28 wεn yuz as di rεprεsεntεtiv pεptida fכ tεst di spεsifisiti כf spadin-analog vs כda K2P chεnal dεm, TREK-2 (A), TRAAK (B), TRESK (C), εn TASK-1 (D).
Di akshɔn we PE22-28 du
Efεkt pan TREK-1 Chanɛl dɛn
in vitro stכdi dεm we yuz patch-klamp tεknכlכji pan hTREK-1/HEK sεl dεm sho se PE22-28 de sho bεtε spεsifisiti εn afiniti fכ TREK-1 chεnal dεm kכmpεr to Spadin. spεsifi k data sho se di IC55 fכ PE22-28 na 0.12 nM, we di wan fכ Spadin na 40–60 nM. dis min se כnda di sem kכndishכn dεm, PE22-28 kin akt pan di TREK-1 chεnal mכr ifektiv wan pan lכw kכnsantreshכn, we de mek i de εksyεrt in bayolojikal ifekt dεm mכr prεsis. di stכdi notis bak se כnda di sem kכndishכn dεm, difrεn modifyushכn dεm na di N- כ C-tεrminus fכ PE22-28 kin mεnten כ εliminet TREK-1 chεnal aktiviti we nכ afekt in afiniti fכ di TREK-1 chεnal. dis yכnik rεgεdyushכn mεkanism fכ chanεl aktiviti εn afiniti de gi imכtant klyu dεm fכ fכda risεch pan in mεkanism fכ akshכn εn dכg divεlכpmεnt.
Antidipreshan ifekt in vivo
Bihayvya mכdel validεshכn: Insay diprεsiv bihayvya mכdel lεk di fכs swim tεst, dεn kכnfכm di antidipreshכn prכpati dεm fכ PE22-28 εn in dεrivεt dεm. Mays we dɛn trit wit Spadin analɔg dɛn (inklud PE22-28) sho se dɛn dɔn ridyus di tɛm we dɛn nɔ de muv. immobilizεshכn tεm na imכtant indikεtכ fכ diprεshכn lεk bihayvya na mays dεm we dεn de fכs swim tεst, εn rεdukshכn pan immobilizεshכn tεm de sho se diprεshכn lεk bihayvya dεn dכn, we sho se PE22-28 gεt antidipreshכn ifekt dεm. In di nכvelti-inhibited fכd tεst afta 4 dez כf sabkrכnik tritmεnt, PE22-28 sכmtεm rεdכks di latεns pεriכd fכ mays fכ kכnsum fכd pεlεt. di novelty-inhibited feeding test na wan εkspεriεns mεtכd fכ ases di mays in wilεns fכ it na nyu envayroment. wan sכt latεns pεriכd de sho se dεn dכn rεdכks di anxiety εn diprεshכn-rεlatεd bihayvya insay mays, fכ kכnfכm di antidipreshכn ifekt dεm fכ PE22-28.
ifekt dεm pan nyurojεnεsis εn sinaptojεnεsis: Afta jכs 4 dez tritmεnt, PE22-28 εn in analכg dεm indyuz nyurojεnεsis, wit G/A-PE22-28 sho patikyula sכm ifekt dεm. Nyurojεnεsis de ple wan kכl rol fכ di patכjεnεsis fכ diprεshכn εn tritmεnt rεspכns, εn di jεnereshכn fכ nyu nyuron dεm de εp fכ impruv nyural fכnshכn εn mכd stet. insay maws kכtikal nyuron dεm, PE22-28 εn in dεrivεt dεm dεn tu εnhans sinaptojεnεsis, as dεn mכsu bay inkrεs PSD-95 εksprεshכn lεvεl dεm. PSD-95 na protin we de asai wit di postsynaptic dense rijyכn, εn di inkrεs εksprεshכn lεvεl dεm de sho se di sinaps fכmeshכn εn fכnshכn de εnhans, we de fεsilit infכmeshכn transmishכn bitwin nyuron dεm εn nyural sεkyut rimכdelin, we na imכpכtant fכ impruv diprεsiv simptom dεm.
di advantej dεm we de fכ di tεm we di akshכn de tek: we yu kכmpεr wit Spadin, di tεm we PE22-28 εn in analכg dεm de tek fכ akshכn de bכku bכku wan. Spadin de lכs in aktiviti 7 awa afta dεn gi am, we di tεm we PE22-28 de akshכn kin rich 23 awa. wan lכng tεm we di akshכn de tek min se in bayolojikal ifekt dεm kin sכstayn fכ lכng tεm in vivo, we de ridyus di frεkuεns fכ administreshכn εn impruv di pasεnt komplians, we gεt imכtant prεktikal implεkshכn fכ klinik tritmεnt.
Aplikeshɔn dɛn fɔ PE22-28
Pכtεnshal aplikεshכn dεm na diprεshכn tritmεnt: Giv PE22-28 in εksεlεnt pεrformεns in antidipreshכn bihayvכral mכdel dεm, in yכnik mεkanism fכ akshכn pan di TREK-1 chεnal, εn in pכsitiv ifekt dεm pan nyurojεnεsis εn sinaptojεnεsis, i rεprεsεnt wan prכmis mכlikul wit di pכtεnshal fכ riples Spadin in diprεshכn tritmεnt. Di we aw PE22-28 kɔmɔt de gi nyu tritmɛnt opshɔn fɔ pwɛl hat. I dɔn bi impɔtant dairekshɔn fɔ di divɛlɔpmɛnt fɔ di nɛks jɛnɛreshɔn fɔ antidipreshɔn drɔgs. Tru mɔ risach ɛn divɛlɔpmɛnt, fɔ optimize in drɔg fɔmyulashɔn ɛn administreshɔn mɛtɔd dɛm, dɛn de ɛkspɛkt fɔ gi mɔ ifektiv tritmɛnt opshɔn fɔ pasɛnt dɛm wae gɛt pwɛl hat.
Usay i kɔmɔt
[1] Djillani A, Pietri M, Moreno S, ɛn ɔda pipul dɛn. Shortened Spadin Analogs Display Bεtε TREK-1 Inhibishכn, In Vivo Stebiliti εn Antidipreshכn Aktiviti[J]. Frɔntiers in Famakɔlɔji, 2017,8:643.DOI:10.3389/fphar.2017.00643.
Prodak we de fɔ yuz fɔ risach nɔmɔ:
