Iphrotheni ye-beta-amyloid (1-42) yabantu, eyaziwa nangokuthi i-Aβ 1-42, iyisici esibalulekile ekuvuleni izimfihlakalo zesifo i-Alzheimer's.Le peptide idlala indima ebalulekile ekwakhekeni kwama-amyloid plaque, amaqoqo angaqondakali alimaza ubuchopho beziguli ze-Alzheimer's.Ngomphumela olimazayo, iphazamisa ukuxhumana kwe-neuronal, ibangele ukuvuvukala, futhi ibangele i-neurotoxicity, okuholela ekukhubazekeni kwengqondo nokulimala kwemizwa.Ukuphenya izindlela zayo zokuhlanganisa kanye nobuthi akubalulekile nje kuphela;wuhambo olujabulisayo olubheke ekuxazululeni iphazili ye-Alzheimer kanye nokuthuthukisa izindlela zokwelapha zesikhathi esizayo.
I-Aβ 1-42 iwucezu lwe-peptide lwama-amino acid angama-42 olususelwa ekuqhekekeni kwe-amyloid precursor protein (APP) nge-β- kanye ne-γ-secretases.I-Aβ 1-42 ingenye yezingxenye eziyinhloko zama-amyloid plaques anqwabelana ebuchosheni beziguli ezinesifo i-Alzheimer's, isifo sezinzwa esibonakala ngokukhubazeka kwengqondo nokulahlekelwa inkumbulo.I-Aβ 1-42 ikhonjiswe ukuthi inemisebenzi ehlukahlukene kanye nezicelo ocwaningweni lwebhayoloji nolwe-biomedical, njengalokhu:
1.I-Neurotoxicity: I-Aβ 1-42 ingenza ama-oligomers ancibilikayo akwazi ukubophezela futhi aphazamise umsebenzi we-neuronal membrane, ama-receptors, nama-synapses.Lawa ma-oligomers angaphinda abangele ukucindezeleka kwe-oxidative, ukuvuvukala, kanye ne-apoptosis kuma-neurons, okuholela ekulahlekelweni kwe-synaptic nokufa kwe-neuronal.I-Aβ 1-42 oligomers ibhekwa njengeneurotoxic kakhulu kunezinye izinhlobo ze-Aβ, njenge-Aβ 1-40, okuwuhlobo oluningi kakhulu lwe-Aβ ebuchosheni.I-Aβ 1-42 oligomers nayo kucatshangwa ukuthi iyakwazi ukusabalala isuka kuseli iye kuseli, efana nama-prions, futhi icuphe ukugoqa nokuhlanganisa amanye amaprotheni, njenge-tau, okwenza ama-neurofibrillary tangles ku-Alzheimer's disease.
I-Aβ 1-42 ithathwa kabanzi njenge-Aβ isoform ene-neurotoxicity ephezulu kakhulu.Ucwaningo oluningi lokuhlola luye lwabonisa i-neurotoxicity ye-Aβ 1-42 kusetshenziswa izindlela namamodeli ahlukene.Isibonelo, uLesné et al.(Brain, 2013) iphenye ukwakheka nobuthi be-Aβ oligomers, okuyizinhlanganisela ezincibilikayo ze-Aβ monomers, futhi yabonisa ukuthi ama-oligomers e-Aβ 1-42 abe nomthelela olimaza kakhulu kuma-neuronal synapses, okuholela ekwehleni kwengqondo nokulahlekelwa yi-neuronal.Lambert et al.(I-Proceedings of the National Academy of Sciences, 1998) yaqokomisa i-neurotoxicity ye-Aβ 1-42 oligomers futhi yathola ukuthi yayinomphumela onamandla onobuthi ohlelweni lwezinzwa oluphakathi, ngokunokwenzeka ngokuthinta ama-synapses nama-neurotransmitters.Walsh et al.(Imvelo, i-2002) ibonise umphumela wokuvimbela we-Aβ 1-42 oligomers ku-hippocampal long-term potentiation (LTP) ku-vivo, okuyindlela yeselula eyisisekelo yokufunda nenkumbulo.Lokhu kuvimbela kwakuhlotshaniswa nokukhubazeka kwenkumbulo nokufunda, kugcizelela umthelela we-Aβ 1-42 oligomers ku-synaptic plasticity.Shankar et al.(Imithi Yemvelo, i-2008) ihlukanise i-Aβ 1-42 dimers ngokuqondile ebuchosheni be-Alzheimer futhi yabonisa umphumela wawo ku-synaptic plasticity kanye nenkumbulo, inikeza ubufakazi obunamandla be-neurotoxicity ye-Aβ 1-42 oligomers.
Ngaphezu kwalokho, u-Su et al.(I-Molecular & Cellular Toxicology, 2019) yenza ukuhlaziywa kwe-transcriptomics kanye ne-proteomics ye-Aβ 1-42-induced neurotoxicity kumaseli e-SH-SY5Y neuroblastoma.Bahlonze izakhi zofuzo eziningana namaprotheni athintwe i-Aβ 1-42 ezindleleni ezihlobene nenqubo ye-apoptotic, ukuhumusha kwamaprotheni, inqubo ye-catabolic ye-cAMP kanye nokusabela ekucindezelekeni kwe-endoplasmic reticulum.Takeda et al.(Biological Trace Element Research, 2020) iphenye indima ye-extracellular Zn2+ ku-Aβ 1-42-induced neurotoxicity ku-Alzheimer's disease.Babonise ukuthi ubuthi be-Aβ 1-42-induced intracellular Zn2+ busheshiswe ngokuguga ngenxa yokwanda okuhlobene neminyaka ku-extracellular Zn2+.Baphakamise ukuthi i-Aβ 1-42 ekhiqizwa ngokuqhubekayo isuka kumatheminali e-neuron idala ukwehla kwengqondo okuhlobene neminyaka kanye nokwakhiwa kwe-neurodegeneration nge-intracellular Zn2+ dysregulation.Lolu cwaningo luphakamisa ukuthi i-Aβ 1-42 iyisici esibalulekile ekulamuleni ubuthi be-neurotoxicity nokuqhubekela phambili kwesifo esifweni se-Alzheimer ngokuthinta izinqubo ezihlukahlukene zamangqamuzana namangqamuzana ebuchosheni.
2. Umsebenzi wokulwa namagciwane: I-Aβ 1-42 kubikwe ukuthi inomsebenzi we-antimicrobial ngokumelene namagciwane ahlukahlukene, afana namagciwane, isikhunta, namagciwane.I-Aβ 1-42 ingabopha futhi iphazamise ulwelwesi lwamangqamuzana amancane, okuholela ku-lysis nokufa kwawo.I-Aβ 1-42 ingakwazi futhi ukusebenzisa amasosha omzimba azalwa nayo futhi ibuthe amaseli avuthayo endaweni yokutheleleka.Olunye ucwaningo luphakamise ukuthi ukunqwabelana kwe-Aβ ebuchosheni kungase kube impendulo evikelayo ezifweni ezingelapheki noma ekulimaleni.Nokho, ukukhiqizwa ngokweqile noma okungalawuleki kwe-Aβ kungase futhi kubangele ukulimala okubambisene kumaseli aphethe kanye nezicubu.
I-Aβ 1-42 kubikwe ukuthi ibonisa umsebenzi wokulwa namagciwane ngokumelene nohlu lwamagciwane, njengamagciwane, isikhunta, namagciwane, njenge-Staphylococcus aureus, i-Escherichia coli, i-Candida albicans, ne-Herpes simplex virus hlobo 1, ngokusebenzisana nolwelwesi lwazo kanye kubangela ukuphazamiseka kwabo kanye ne-lysis.Kumar et al.(I-Journal of Alzheimer's Disease, 2016) ibonise lo mphumela ngokubonisa ukuthi i-Aβ 1-42 iguqule ulwelwesi lokungena kanye nokwakheka kwamangqamuzana amancane, okuholela ekufeni kwawo.Ngokungeziwe esenzweni sayo esiqondile se-antimicrobial, i-Aβ 1-42 ingaphinda iguqule ukusabela kokuzivikela komzimba okungaphakathi futhi ibuthe amaseli avuthayo endaweni yokutheleleka.Soscia et al.(i-PLoS One, i-2010) iveze le ndima ngokubika ukuthi i-Aβ 1-42 igqugquzele ukukhiqizwa kwama-cytokines ane-pro-inflammatory nama-chemokines, njenge-interleukin-6 (IL-6), i-tumor necrosis factor-alpha (TNF-α), i-monocyte i-chemoattractant protein-1 (MCP-1), kanye ne-macrophage inflammatory protein-1 alpha (MIP-1α), ku-microglia kanye ne-astrocytes, amangqamuzana omzimba omzimba amakhulu ebuchosheni.
Umfanekiso 2. Ama-Aβ peptide anomsebenzi we-antimicrobial.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. I-Alzheimer's-associated amyloid beta-protein iyi-peptide elwa namagciwane. PLoS One . 2010 Mar 3;5(3):e9505.)
Nakuba olunye ucwaningo luye lwaphakamisa ukuthi ukunqwabelana kwe-Aβ ebuchosheni kungase kube impendulo evikelayo ezifweni noma ekulimaleni okungapheli, njengoba i-Aβ ingakwazi ukusebenza njenge-antimicrobial peptide (AMP) futhi iqede amagciwane angaba khona, ukusebenzisana okuyinkimbinkimbi phakathi kwe-Aβ kanye nezakhi ezincane ze-microbial kusalokhu kungumphumela. isihloko sophenyo.Ibhalansi ethambile iqokonyiswa ucwaningo lukaMoir et al.(Journal of Alzheimer's Disease, 2018), ephakamisa ukuthi ukukhiqizwa kwe-Aβ okungalingani noma okweqile kungalimaza amaseli aphethe nezicubu, okubonisa ubumbaxambili obuyinkimbinkimbi bendima ye-Aβ ekuthelelekeni nasekuwohlokeni kwemizwa.Ukukhiqizwa okweqile noma okungasebenzi kahle kwe-Aβ kungase kuholele ekuhlanganisweni nasekubekweni kwayo ebuchosheni, kwakheka ama-oligomer anobuthi nama-fibril akhubaza ukusebenza kwe-neuronal futhi abangele i-neuroinflammation.Lezi zinqubo ze-pathological zihlotshaniswa nokuncipha kwengqondo nokulahlekelwa inkumbulo esifweni i-Alzheimer's, isifo se-neurodegenerative esibonakala ngokuwohloka komqondo okuqhubekayo.Ngakho-ke, ibhalansi phakathi kwemiphumela ezuzisayo nelimazayo ye-Aβ ibalulekile ekugcineni impilo yobuchopho nokuvimbela ukuwohloka kwezinzwa.
3.Ukuthekelisa okusansimbi: I-Aβ 1-42 ikhonjiswe ukuthi iyabandakanyeka ekulawulweni kwe-iron homeostasis ebuchosheni.I-ayoni iyisici esibalulekile ezinqubweni eziningi zebhayoloji, kodwa i-ayoni eyeqile nayo ingadala ingcindezi ye-oxidative kanye ne-neurodegeneration.I-Aβ 1-42 ingabophezela ku-ayoni futhi yenze kube lula ukuthunyelwa kwayo kusuka kuma-neuron nge-ferroportin, isithuthi sensimbi ye-transmembrane.Lokhu kungasiza ekuvimbeleni ukunqwabelana kwe-iron kanye nobuthi ebuchosheni, njengoba i-iron eyeqile ingabangela ingcindezi ye-oxidative kanye ne-neurodegeneration.Duce et al.(Iseli, i-2010) ibike ukuthi i-Aβ 1-42 iboshelwe ku-ferroportin futhi yandisa inkulumo yayo nomsebenzi kuma-neuron, okuholela ekwehleni kwamazinga ensimbi e-intracellular.Baphinde babonisa ukuthi i-Aβ 1-42 yehlise ukuvezwa kwe-hepcidin, ihomoni evimbela i-ferroportin, kuma-astrocyte, ethuthukisa ukuthunyelwa kwensimbi kuma-neuron.Kodwa-ke, i-Aβ eboshwe ngensimbi ingase ijwayele ukuhlangana futhi ifakwe endaweni engaphandle kwamangqamuzana, yenze ama-amyloid plaque.Ayton et al.(I-Journal of Biological Chemistry, i-2015) ibike ukuthi insimbi ikhuthaze ukwakheka kwe-Aβ oligomers nama-fibrils in vitro kanye ne-vivo.Baphinde bakhombisa ukuthi i-iron chelation yehlise ukuhlangana kwe-Aβ kanye nokufakwa kumagundane ashintshashintshayo.Ngakho-ke, ibhalansi phakathi kwemiphumela ezuzisayo nelimazayo ye-Aβ 1-42 ku-iron homeostasis ibalulekile ekugcineni impilo yobuchopho nokuvimbela ukuwohloka kwemizwa.
Singumkhiqizi we-polypeptide e-China, esineminyaka eminingana yokuhlangenwe nakho okuvuthiwe ekukhiqizeni i-polypeptide.I-Hangzhou Taijia Biotech Co., Ltd. ingumkhiqizi wezinto ezingavuthiwe ze-polypeptide, enganikeza amashumi ezinkulungwane zezinto zokusetshenziswa ze-polypeptide futhi ingenziwa ngokwezifiso ngokwezidingo.Izinga lemikhiqizo ye-polypeptide lihle kakhulu, futhi ubumsulwa bungafinyelela ku-98%, okuye kwaqashelwa abasebenzisi emhlabeni wonke.Siyakwamukela ukuthi uxhumane nathi.
