Barootiinka beta-amyloid (1-42), oo sidoo kale loo yaqaan Aβ 1-42, waa arrin muhiim ah oo furaysa siraha cudurka Alzheimers.Peptide-kani waxa uu kaalin dhexe ka ciyaaraa samaynta huurada amyloid, rucubyada hal-abuurka leh ee waxyeelleeya maskaxda bukaanka Alzheimers.Iyada oo saameyn xun leh, waxay carqaladeysaa isgaadhsiinta neerfaha, waxay kicisaa caabuqa, waxayna keentaa neurotoxicity, taasoo keenta cillad garashada iyo dhaawaca neerfaha.Baarista habka isu geynta iyo sunta ma aha oo kaliya muhiim;waa safar xiiso leh oo lagu xallinayo halxiraalaha Alzheimers iyo horumarinta daawaynta mustaqbalka.
Aβ 1-42 waa jajab peptide ah oo ka kooban 42 amino acids kaas oo ka soo jeeda jeexjeexa borotiinka amyloid precursor (APP) by β- iyo γ-sirta.Aβ 1-42 waa mid ka mid ah qaybaha ugu muhiimsan ee looxyada amyloid ee ku urura maskaxda bukaanada qaba cudurka Alzheimers, cillad neurodegenerative oo lagu garto cillad xagga garashada iyo lumista xusuusta.Aβ 1-42 ayaa la muujiyey inay leedahay hawlo iyo codsiyo kala duwan oo ku saabsan cilmi-baarista bayoolojiga iyo bayoolajiga, sida:
1. Neurotoxicity: Aβ 1-42 waxay samayn kartaa oligomers milmi kara kuwaas oo awood u leh inay ku xidhaan oo ay carqaladeeyaan shaqada xuubabka neuronal, reseptors, iyo synapses.Oligomers-yadani waxay sidoo kale keeni karaan diiqad oksaydh ah, barar, iyo apoptosis ee neerfayaasha, taasoo keenta luminta synaptik iyo dhimashada neerfaha.Aβ 1-42 oligomers waxaa loo tixgeliyaa inay yihiin kuwo neurotoxic ah marka loo eego noocyada kale ee Aβ, sida Aβ 1-40, oo ah qaabka ugu badan ee Aβ ee maskaxda.Aβ 1-42 oligomers ayaa sidoo kale loo maleynayaa inay awoodaan inay ku faafiyaan unug ilaa unug, oo la mid ah prions, oo ay kiciyaan isku-duubnaanta iyo isku-darka borotiinnada kale, sida tau, kaas oo sameeya tangles neurofibrillary ee cudurka Alzheimers.
Aβ 1-42 waxaa loo arkaa inay tahay Aβ isoform oo leh neurotoxicity ugu sarreeya.Daraasado dhowr ah oo tijaabo ah ayaa muujiyay neurotoxicity Aβ 1-42 iyadoo la adeegsanayo habab iyo qaabab kala duwan.Tusaale ahaan, Lesné et al.(Brain, 2013) ayaa baadhay samaynta iyo sunta Aβ oligomers, kuwaas oo ah isku-darka isku-darka ah ee Aβ monomers, waxayna muujiyeen in Aβ 1-42 oligomers ay saameyn xoog leh ku yeesheen synapses neuronal, taasoo keentay hoos u dhaca garashada iyo luminta neuronal.Lambert iyo al.(Tallaabooyinka Akadeemiyada Qaranka ee Sayniska, 1998) ayaa iftiimiyay neurotoxicity ee Aβ 1-42 oligomers waxayna ogaadeen in ay saameyn xooggan ku yeesheen habka dhexe ee neerfayaasha, laga yaabo inay saameeyaan synapses iyo neurotransmitters.Walsh iyo al.(Dabeecadda, 2002) waxay muujisay saameynta xannibaadda ee Aβ 1-42 oligomers ee awoodda muddada dheer ee hippocampal (LTP) ee vivo, taas oo ah habka gacanta ee hoosta waxbarashada iyo xusuusta.Joojintaani waxay la xiriirtaa xusuusta iyo waxbarashada liidata, iyada oo xoogga saareysa saameynta Aβ 1-42 oligomers ee balaastikada synaptik.Shankar iyo al.(Daawaynta Dabeecadda, 2008) Aβ 1-42 dimers si toos ah uga soo jeeda maskaxda Alzheimers waxayna muujiyeen saameyntooda balaastikada synaptik iyo xusuusta, iyagoo siinaya caddayn macquul ah oo ku saabsan neurotoxicity Aβ 1-42 oligomers.
Intaa waxaa dheer, Su et al.(Molecular & Cellular Toxicology, 2019) waxay sameeyeen transcriptomics iyo falanqaynta boroteomics ee Aβ 1-42-ku-takoorka neurotoxicity ee unugyada SH-SY5Y neuroblastoma.Waxay aqoonsadeen dhowr hidde-side iyo borotiinno ay saameeyeen Aβ 1-42 waddooyinka la xiriira habka apoptotic, tarjumaadda borotiinka, habka catabolic cAMP iyo jawaabta diiqada endoplasmic reticulum.Takeda iyo al.(Cilmi-baadhista Cunsurka Nafleyda, 2020) waxay baadhay doorka Zn2+ ee ka baxsan unugyada Aβ 1-42 ee neurotoxicity ee cudurka Alzheimers.Waxay muujiyeen in Aβ 1-42-ku-soo-baxa intracellular Zn2+ suntan la dedejiyey gabowga sababtoo ah kororka da'da la xiriirta ee Zn2+ ee ka baxsan unugyada.Waxay soo jeediyeen in Aβ 1-42 ay si joogto ah uga soo baxdo terminaalka neuronku ay keento hoos u dhaca garashada da'da ee la xiriirta da'da iyo neurodegeneration iyada oo loo marayo intracellular Zn2 + dysregulation.Daraasadahaani waxay soo jeedinayaan in Aβ 1-42 ay tahay arrin muhiim ah oo dhexdhexaadinaysa neurotoxicity iyo horumarka cudurka ee cudurka Alzheimers iyadoo saameynaysa hababka kala duwan ee unugyada iyo unugyada maskaxda ee maskaxda.
2. Dhaqdhaqaaqa ka hortagga jeermiska: Aβ 1-42 ayaa lagu soo warramey inay leedahay firfircooni antimicrobial oo ka dhan ah cudur-sidaha kala duwan, sida bakteeriyada, fungi, iyo fayrasyada.Aβ 1-42 waxay xiri kartaa oo carqaladeyn kartaa xuubka unugyada microbial, taasoo u horseedaysa lysis iyo dhimasho.Aβ 1-42 waxay sidoo kale kicin kartaa habka difaaca jirka oo ay qorto unugyo barar ah goobta caabuqa.Daraasadaha qaarkood ayaa soo jeediyay in ururinta Aβ ee maskaxda ay noqon karto jawaab celin ka hortag ah caabuqyada ama dhaawacyada joogtada ah.Si kastaba ha ahaatee, wax soo saarka xad-dhaafka ah ama habacsanaanta ee Aβ waxay sidoo kale keeni kartaa dhaawac dammaanad ah oo ku yimaada unugyada iyo unugyada martida loo yahay.
Aβ 1-42 ayaa lagu soo warramey inay muujiso waxqabadka antimicrobial ka dhan ah noocyo kala duwan oo cudur-sidaha, sida bakteeriyada, fungi, iyo fayrasyada, sida Staphylococcus aureus, Escherichia coli, Candida albicans, iyo Herpes simplex fayraska nooca 1, iyagoo la falgalaya xuubkooda iyo taasoo keenaysa khalkhalkooda iyo lysiskooda.Kumar iyo al.(Journal of Alzheimer's Disease, 2016) ayaa muujisay saamayntan iyada oo muujinaysa in Aβ 1-42 ay beddeshay xuubka xuubka iyo qaabka unugyada microbial, taasoo keentay dhimashadooda.Marka lagu daro ficilkeeda tooska ah ee antimicrobial, Aβ 1-42 waxay sidoo kale wax ka beddeli kartaa jawaabta difaaca jirka oo ay qorto unugyada caabuqa goobta caabuqa.Soscia iyo al.(PLoS One, 2010) ayaa shaaca ka qaaday doorkan iyadoo la soo sheegay in Aβ 1-42 ay kicisay wax soo saarka cytokines pro-inflammatory iyo chemokines, sida interleukin-6 (IL-6), factor necrosis factor-alpha (TNF-α), monocyte. chemoattractant protein-1 (MCP-1), iyo macrophage inflammatory protein-1 alpha (MIP-1α), ee microglia iyo astrocytes, unugyada difaaca ugu weyn ee maskaxda.
Jaantuska 2. Aβ peptides waxay leeyihiin firfircoonida ka hortagga jeermiska.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M. Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD 2010 Mar 3;5(3):e9505.)
Inkastoo cilmi-baarisyada qaarkood ay soo jeediyeen in ururinta Aβ ee maskaxda ay noqon karto jawaab celin ka hortag ah caabuqyada ama dhaawacyada daba-dheeraada, maadaama Aβ ay u dhaqmi karto sidii peptide antimicrobial (AMP) oo ay tirtirto cudur-sidaha suurtagalka ah, isdhexgalka adag ee u dhexeeya Aβ iyo walxaha microbial ayaa weli ah mawduuca baaritaanka.Isku-dheelitirka jilicsan ayaa lagu muujiyay cilmi-baarista Moir et al.(Journal of Alzheimer's Disease, 2018), kaas oo soo jeedinaya in dheellitir la'aanta ama soo-saarka Aβ ee xad-dhaafka ah ay si ula kac ah u waxyeeleyso unugyada iyo unugyada martida loo yahay, taasoo ka tarjumaysa dabeecadda adag ee dual ee doorka Aβ ee caabuqa iyo neurodegeneration.Wax-soo-saarka xad-dhaafka ah ama cilladaysan ee Aβ waxay u horseedi kartaa isku-ururinteeda iyo ku-tiirsanaanta maskaxda, samaynta oligomers sun ah iyo fibrils kuwaas oo wax u dhimaya shaqada neerfaha oo keena neuroinflammation.Nidaamyadaan cudurrada faafa waxay la xiriiraan hoos u dhaca garashada iyo luminta xusuusta ee cudurka Alzheimers, cillad neurodegenerative oo lagu garto waallida sii socota.Sidaa darteed, dheelitirka u dhexeeya faa'iidada iyo waxyeelada waxtarka leh ee Aβ ayaa muhiim u ah ilaalinta caafimaadka maskaxda iyo ka hortagga neurodegeneration.
3.Birta dhoofinta: Aβ 1-42 ayaa la muujiyey inay ku lug leedahay nidaaminta homeostasis birta ee maskaxda.Birtu waa shay lagama maarmaan u ah habab badan oo bayooloji ah, laakiin birta xad-dhaafka ah waxay sidoo kale sababi kartaa walbahaarka oksaydhka iyo neerfayaasha.Aβ 1-42 waxay ku xidhi kartaa birta waxayna fududayn kartaa dhoofinta neerfaha iyada oo loo marayo ferroportin, gaadiidka birta ee transmembrane.Tani waxay kaa caawin kartaa ka hortagga ururinta birta iyo sunta maskaxda, maadaama birta xad-dhaafka ah ay sababi karto walbahaarka oksaydhka iyo neerfayaasha.Duce iyo al.(Cell, 2010) ayaa sheegay in Aβ 1-42 ay ku xiran tahay ferroportin oo ay kordhisay muujinteeda iyo dhaqdhaqaaqa neerfaha, taasoo keentay hoos u dhaca heerarka birta unugyada.Waxay sidoo kale muujiyeen in Aβ 1-42 ay hoos u dhigtay muujinta hepcidin, hormoonka joojiya ferroportin, ee astrocytes, sii wanaajinta dhoofinta birta ee neurons.Si kastaba ha ahaatee, Aβ-ku-xidhan birtu waxay sidoo kale noqon kartaa mid aad ugu nugul isku-ururinta iyo dhigista meel bannaan oo ka baxsan, samaynta lakabyo amyloid ah.Ayton iyo al.(Journal of Biological Chemistry, 2015) ayaa sheegay in birta ay kor u qaaday samaynta Aβ oligomers iyo fibrils in vitro iyo in vivo.Waxay sidoo kale muujiyeen in chelation-ka birta ay hoos u dhigtay isku-darka Aβ iyo dhigista jiirarka transgenic.Sidaa darteed, dheelitirka u dhexeeya faa'iidada iyo waxyeelada Aβ 1-42 ee homeostasis birta ayaa muhiim u ah ilaalinta caafimaadka maskaxda iyo ka hortagga neurodegeneration.
Waxaan nahay soo saaraha polypeptide ee Shiinaha, oo leh dhowr sano oo waayo-aragnimo ah oo bislaaday wax soo saarka polypeptide.Hangzhou Taijia Biotech Co., Ltd. waa xirfadle soo saaraha alaabta ceeriin polypeptide, kaas oo ku siin kara tobanaan kun oo polypeptide alaabta ceeriin iyo sidoo kale loo habayn karaa iyadoo loo eegayo baahiyaha.Tayada alaabada polypeptide waa mid aad u fiican, nadiifintuna waxay gaari kartaa 98%, taas oo ay aqoonsadeen isticmaalayaasha adduunka oo dhan. Ku soo dhawow inaad nala tashato.
