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Oreksin angl Hypocretin neuropeptide precursor HCRT bilok yakij koduyetsya odnojmennim genom roztashovanim u lyudej na dovgomu plechi 17 yi hromosomi 17q21 2 1 Dovzhina polipeptidnogo lancyuga bilka stanovit 131 aminokislot a molekulyarna masa 13 363 Da 2 HCRTIdentifikatoriSimvoliHCRTNRCLP1OXPPOXhypocretin orexin neuropeptide precursorhypocretin neuropeptide precursorZovnishni ID GeneCards 1 OrtologiVidi Lyudina MishaEntrezn d n dEnsembl n d n dUniProt n d n dRefSeq mRNK n dn dRefSeq bilok n dn dLokus UCSC n dn dPubMed search n dn dVikidaniDiv Red dlya lyudejPoslidovnist aminokislot1020304050MNLPSTKVSWAAVTLLLLLLLLPPALLSSGAAAQPLPDCCRQKTCSCRLYELLHGAGNHAAGILTLGKRRSGPPGLQGRLQRLLQASGNHAAGILTMGRRAGAEPAPRPCLGRRCSAPAAASVAPGGQSGIA Alanin C Cisteyin D Asparaginova kislota E Glutaminova kislota G Glicin H Gistidin I Izolejcin K Lizin L Lejcin M Metionin N Asparagin P Prolin Q Glutamin R Arginin S Serin T Treonin V Valin W Triptofan Y TirozinDva oreksini Oreksin A i Oreksin B mayut 50 vidsotkovu gomologiyu poslidovnosti ne mayuchi pri comu znachnoyi gomologiyi z inshimi peptidami v organizmi Oreksini sintezuyutsya porivnyano nevelikoyu populyaciyeyu klitin lateralnogo gipotalamusa blizko 50000 3 chiyi aksoni dosyagayut praktichno vsih regioniv mozku Vvazhayetsya sho nestacha oreksinu v mozku prizvodit do rozvitku narkolepsiyi Oreksini demonstruyut silno zberezhenu poslidovnist aminokislot i znajdeni u vsih hrebetnih sho vkazuye na yih rannyu poyavu v evolyuciyi hrebetnih Lokalizovanij u klitinnih kontaktah endoplazmatichnomu retikulumi citoplazmatichnih vezikulah sinapsah Sintezuyetsya v serci placenti legenyah pechinci skeletnih m yazah nirkah ta pidshlunkovij zalozi Oreksin buv viyavlenij v 1998 roci majzhe odnochasno dvoma nezalezhnimi grupami doslidnikiv mozku shuriv 4 5 Odna grupa nazvala jogo oreksinom vid orexis sho z greckoyi perekladayetsya apetit a insha grupa gipokratinom tomu sho vin sintezuyetsya v gipotalamusi i neznachno shozhij z inshim peptidom sekretinom Zmist 1 Budova 2 Funkciyi 2 1 Son 2 2 Regulyuvannya energetichnogo balansu 2 3 Efekti v periferichnih tkaninah 2 4 Uchast v procesah rozvitku zalezhnosti i zvikannya 3 Potencijni napryamki zastosuvannya 4 Literatura 5 Primitki 6 Div takozhBudova Redaguvati nbsp Stuktura prepro oreksinuGen prepro oreksinu lyudini 1432 p n skladayetsya z dvoh ekzoniv ta odnogo intronu Pershij ekzon 143 p n vklyuchaye 5 netranslovanu oblast ta neveliku chastinu koduyuchoyi oblasti yaka koduye pershi sim zalishkiv sekretornoyi signalnoyi poslidovnosti Drugij ekzon mistit zalishkovu chastinu vidkritoyi ramki zchituvannya ta 3 netranslovanu oblast 6 Promotor genu Hcrt ye klyuchovim elementom regulyuvannya ekspresiyi oreksinu v populyaciyi nejroniv gipotalamusu Promotor mistit sajti yaki stimulyuyut ta obmezhuyut ekspresiyu prepro oreksinu vklyuchayuchi regulyuyuchi elementi 1 i 2 OE1 ta OE2 Sajt OE1 pereshkodzhaye ekspresiyi geniv Hcrt poza gipotalamusom Oblast sho znahoditsya vishe vid miscya zapusku transkripciyi mistit neobhidni elementi pravilnoyi ekspresiyi ta zv yazuvannya dekilkoh faktoriv transkripciyi vklyuchayuchi box A2 Foxa2 IGFBP3 ta yaderni receptori sho stimulyuyut abo prignichuyut ekspresiyu genu Hcrt 7 Pokazano sho mRNK prepro oreksinu regulyuyetsya pid chas goloduvannya sho svidchit pro te sho ci nejroni vidchuvayut energetichnij balans tvarini Kilka zvitiv pokazali sho oreksinovi nejroni ekspresuyut receptori leptinu ta regulyuyutsya nim Tomu znizhennya rivnya leptinu mozhe buti mozhlivim faktorom sho pidvishuye riven ekspresiyi mRNK prepro orekinu pid chas goloduvannya Riven prepro oreksinu takozh pidvishuvavsya pri gipoglikemichnih stanah sho svidchit pro te sho ekspresiya genu prepro oreksinu takozh regulyuyetsya rivnem glyukozi v plazmi 8 Bilok prepro oreksin yakij maye tipovu sekretornu signalnu poslidovnist na jogo N kinci proteolitichno rozsheplyuyetsya z utvorennyam zrilih oreksiniv A ta B 9 Oreksin A dovzhinoyu v 33 aminokisloti i maye dva disulfidni zv yazki Cys6 Cys12 Cys7 Cys14 neobhidni dlya jogo funkcionuvannya Oreksin B pryamij lancyug z 28 aminokislot Oreksin A maye priblizno odnakovu afinnist do oboh receptoriv v toj chas yak Oreksin B reaguye v osnovnomu z OX2 i v 5 raziv slabshe oreksinu A 10 Isnuyut dva oreksinovi receptori OX1 and OX2 Voni ye G bilokspryazhenimi receptorami Funkciyi RedaguvatiSon Redaguvati Osnovnoyu funkciyeyu oreksinu ye pidtrimka stanu nespannya Endogenna nestacha oreksinu prizvodit do narkolepsiyi zahvoryuvannya sho harakterizuyetsya porushennyami cikliv snu nespannya 3 11 Tochkovi mutaciyi v geni Oreksin buli viyavleni yak prichina deyakih rozladiv snu Regulyuvannya energetichnogo balansu Redaguvati Pri sposterezhenni za lyudmi i tvarinami sho strazhdayut narkolepsiyeyu bula vidznachena shilnist do povnoti i ozhirinnya hocha apetit pri comu znizhuvavsya Doslidi na mishah dozvolili vchenim zrobiti visnovok sho oreksini pidvishuyut odnochasno i apetit i bazalnij riven metabolizmu Efekti v periferichnih tkaninah Redaguvati Vidomo vpliv oreksinu na riven cukru v krovi metabolizm v zhirovih tkaninah krov yanij tisk pidvishuye i ovulyaciyu 12 Uchast v procesah rozvitku zalezhnosti i zvikannya Redaguvati Oreksini zajmayut centralne misce v mezolimbichnih i mezokortikalnih shlyahah v mozku sho vidpovidayut za viroblennya motivovanoyi povedinki i poyavu psihologichnoyi zalezhnosti Vidomo pro vzayemodiyu oreksinu nejroniv z dilyankoyu VTA ventral tegmental area yaka robit mozhlivoyu nejronnu plastichnist pov yazanu z procesom zalezhnosti Aktivaciya ciyeyi sistemi mozhe vidnoviti povedinku spryamovanu na otrimannya zadovolennya vid narkotiku cherez dovgij chas pislya pripinennya jogo prijomu 13 Potencijni napryamki zastosuvannya RedaguvatiOreksin zdatnij pokrashuvati kognitivni funkciyi mozku u primativ osoblivo v umovah pozbavlennya snu 14 sho mozhe zabezpechiti mozhlivist likuvannya nadmirnoyi sonlivosti vden 15 Doslidzhennya pokazali sho transplantaciya nejroniv sho sintezuyut oreksin v retikulyarnu formaciyu u pacyukiv ye mozhlivoyu Ce svidchit pro potecijnu rozrobku alternativnih terapevtichnih strategij dlya likuvannya narkolepsiyi 16 Sogodni rozroblyayutsya yak agonisti oreksinu dlya likuvannya narkolepsiyi tak i antagonisti dlya likuvannya bezsonnya Eksperimenti pokazali sho efektivnist intranazalnogo prijomu oreksinu ne postupayetsya vnutrishnovennomu prijomu za efektom 17 Literatura RedaguvatiHungs M Mignot E 2001 Hypocretin orexin sleep and narcolepsy Bioessays 23 397 408 PubMed DOI 10 1002 bies 1058 Willie J T Chemelli R M Sinton C M Yanagisawa M 2001 To eat or to sleep Orexin in the regulation of feeding and wakefulness Annu Rev Neurosci 24 429 458 PubMed DOI 10 1146 annurev neuro 24 1 429 Kim H Y Hong E Kim J I Lee W 2004 Solution structure of human orexin A regulator of appetite and wakefulness J Biochem Mol Biol 37 565 573 PubMed DOI 10 5483 BMBRep 2004 37 5 565Primitki Redaguvati HUGO Gene Nomenclature Commitee HGNC 4847 angl Arhiv originalu za 13 chervnya 2017 Procitovano 21 veresnya 2017 UniProt O43612 angl Arhiv originalu za 8 serpnya 2017 Procitovano 21 veresnya 2017 a b Kousaku Ohno and Takeshi Sakurai Orexin neuronal circuitry Role in the regulation of sleep and wakefulness Frontiers in Neuroendocrinology T 29 1 January 2008 S 70 87 Sakurai Takeshi Amemiya Akira Ishii Makoto Matsuzaki Ichiyo Chemelli Richard M Tanaka Hirokazu Williams S Clay Richardson James A ta in Orexins and Orexin Receptors A Family of Hypothalamic Neuropeptides and G Protein Coupled Receptors that Regulate Feeding Behavior Cell 92 4 s 573 585 doi 10 1016 s0092 8674 00 80949 6 Arhiv originalu za 16 sichnya 2018 Procitovano 15 sichnya 2018 rekomenduyetsya displayauthors dovidka Lecea L de Kilduff T S Peyron C Gao X B Foye P E Danielson P E Fukuhara C Battenberg E L F ta in 6 sichnya 1998 The hypocretins Hypothalamus specific peptides with neuroexcitatory activity Proceedings of the National Academy of Sciences angl 95 1 s 322 327 ISSN 0027 8424 PMID 9419374 doi 10 1073 pnas 95 1 322 Arhiv originalu za 30 chervnya 2015 Procitovano 15 sichnya 2018 rekomenduyetsya displayauthors dovidka Sakurai T Moriguchi T Furuya K Kajiwara N Nakamura T Yanagisawa M Goto K 18 chervnya 1999 Structure and function of human prepro orexin gene The Journal of Biological Chemistry 274 25 s 17771 17776 ISSN 0021 9258 PMID 10364220 Arhiv originalu za 27 sichnya 2018 Procitovano 21 sichnya 2018 Si nchez Garci a Adriana Cabral Pacheco Griselda Zomosa Signoret Viviana Ortiz Li pez Roci o Camacho Alberto Tabera Tarello Paulo Garnica Li pez Josi Vidaltamayo Romi n 1 lyutogo 2018 Modular organization of a hypocretin gene minimal promoter Molecular Medicine Reports 17 2 ISSN 1791 2997 doi 10 3892 mmr 2017 8142 Arhiv originalu za 24 sichnya 2018 Procitovano 23 sichnya 2018 Ohno Kousaku Sakurai Takeshi January 2008 Orexin neuronal circuitry role in the regulation of sleep and wakefulness Frontiers in Neuroendocrinology 29 1 s 70 87 ISSN 1095 6808 PMID 17910982 doi 10 1016 j yfrne 2007 08 001 Arhiv originalu za 31 sichnya 2018 Procitovano 23 sichnya 2018 Sakurai Takeshi Reverse pharmacology of orexin from an orphan GPCR to integrative physiology Regulatory Peptides 126 1 2 s 3 10 doi 10 1016 j regpep 2004 08 006 Arhiv originalu za 24 sichnya 2018 Procitovano 23 sichnya 2018 T Sakurai Reverse pharmacology of orexin from an orphan GPCR to integrative physiology Regulatory peptides 126 2005 C 3 10 Thomas Chacko Thannickal A decade of hypocretin orexin Accomplishments in sleep medicine Sleep Medicine Reviews T 13 1 February 2009 S 5 8 M V Heinonen et al Functions of orexins in peripheral tissues Acta Physiologica T 192 4 S 471 485 R Preedy Victor Ross Watson Ronald R Ronald 1964 Martin Colin R 2011 Handbook of behavior food and nutrition New York Springer ISBN 9780387922713 OCLC 728098383 Nixon Joshua P Mavanji Vijayakumar Butterick Tammy A Billington Charles J Kotz Catherine M Teske Jennifer A Sleep disorders obesity and aging The role of orexin Ageing Research Reviews 20 s 63 73 doi 10 1016 j arr 2014 11 001 Arhiv originalu za 16 sichnya 2018 Procitovano 15 sichnya 2018 Billiard Michel June 2008 Narcolepsy current treatment options and future approaches Neuropsychiatric Disease and Treatment 4 3 s 557 566 ISSN 1176 6328 PMC PMC2526380 PMID 18830438 Arhiv originalu za 16 sichnya 2018 Procitovano 15 sichnya 2018 Arias Carrion Oscar Murillo Rodriguez Eric Xu Man Blanco Centurion Carlos Drucker Colin Rene Shiromani Priyattam J 15 grudnya 2004 Transplantation of hypocretin neurons into the pontine reticular formation preliminary results Sleep 27 8 s 1465 1470 ISSN 0161 8105 PMC PMC1201562 PMID 15683135 Arhiv originalu za 1 chervnya 2018 Procitovano 15 sichnya 2018 SV Dhuria LR Hanson WH Frey Intranasal drug targeting of hypocretin 1 orexin A to the central nervous system II Journal of Pharmaceutical Sciences 2008 interscience wiley comDiv takozh RedaguvatiHromosoma 17 nbsp Ce nezavershena stattya pro bilki Vi mozhete dopomogti proyektu vipravivshi abo dopisavshi yiyi Otrimano z https uk wikipedia org w index php title HCRT amp oldid 40472458