Batho ba beta-amyloid (1-42) protheine, e tsejoang hape e le Aβ 1-42, ke ntlha ea bohlokoa ho notlolleng liphiri tsa lefu la Alzheimer.Peptide ena e bapala karolo ea mantlha ho thehoeng ha li-amyloid plaques, lihlopha tse makatsang tse senyang boko ba bakuli ba Alzheimer's.Ka phello e senyang, e sitisa puisano ea methapo ea kutlo, e baka ho ruruha, 'me e baka neurotoxicity, e lebisang ho senyeha ha kelello le ho senyeha ha methapo.Ho batlisisa mekhoa ea eona ea ho kopanya le chefo ha ho bohlokoa feela;ke leeto le monate la ho rarolla bothata ba Alzheimer le ho nts'etsapele liphekolo tsa kamoso.
Aβ 1-42 ke sekhechana sa peptide sa 42 amino acid e nkiloeng ho petsoha ha amyloid precursor protein (APP) ka β- le γ-secretases.Aβ 1-42 ke e 'ngoe ea likarolo tse ka sehloohong tsa li-amyloid plaque tse bokellanang bokong ba bakuli ba nang le lefu la Alzheimer's, lefu la neurodegenerative le khetholloang ke ho senyeha ha kelello le ho lahleheloa ke mohopolo.Aβ 1-42 e bonts'itsoe e na le mesebetsi le ts'ebeliso e fapaneng lipatlisisong tsa bioloji le tsa biomedical, joalo ka:
1. Neurotoxicity: Aβ 1-42 e ka etsa li-oligomers tse qhibilihang tse khonang ho tlama le ho senya ts'ebetso ea li-membrane tsa neuronal, li-receptor le li-synapse.Li-oligomers tsena li ka boela tsa baka khatello ea oxidative, ho ruruha, le apoptosis ho li-neuron, tse lebisang tahlehelong ea synaptic le lefu la neuronal.Aβ 1-42 oligomers e nkuoa e le neurotoxic ho feta mefuta e meng ea Aβ, joalo ka Aβ 1-40, e leng mofuta o mongata oa Aβ bokong.Li-oligomers tsa Aβ 1-42 le tsona ho nahanoa hore li khona ho hasana ho tloha seleng ho ea ho sele, ho tšoana le li-prions, 'me li baka ho senyeha le ho bokellana ha liprotheine tse ling, tse kang tau, tse etsang li-neurofibrillary tangles ho lefu la Alzheimer's.
Aβ 1-42 e nkoa e le Aβ isoform e nang le neurotoxicity e phahameng ka ho fetisisa.Lithuto tse 'maloa tsa liteko li bonts'itse neurotoxicity ea Aβ 1-42 ho sebelisoa mekhoa le mefuta e fapaneng.Ka mohlala, Lesné et al.(Brain, 2013) e ile ea etsa lipatlisiso ka sebopeho le chefo ea li-oligomers tsa Aβ, e leng likarolo tse qhibilihang tsa Aβ monomers, 'me tsa bontša hore li-oligomers tsa Aβ 1-42 li na le phello e matla e senyang li-neuronal synapses, tse lebisang ho fokotseha ha kelello le ho lahleheloa ke neuronal.Lambert le ba bang.(Proceedings of the National Academy of Sciences, 1998) e ile ea totobatsa neurotoxicity ea Aβ 1-42 oligomers 'me ea fumana hore e na le phello e matla ea chefo tsamaisong ea methapo e bohareng, mohlomong ka ho ama li-synapse le li-neurotransmitters.Walsh et al.(Nature, 2002) e bontšitse phello ea inhibitory ea Aβ 1-42 oligomers ho hippocampal nako e telele potentiation (LTP) ka vivo, e leng mochine oa cellular o thehiloeng ho ithuta le ho hopola.Thibelo ena e ne e amahanngoa le ho senyeha ha mohopolo le ho ithuta, ho hatisa phello ea li-oligomers tsa Aβ 1-42 ho polasetiki ea synaptic.Shankar et al.(Nature Medicine, 2008) e arolelitse Aβ 1-42 dimers ka ho toba ho tloha bokong ba Alzheimer' me ea bontša phello ea eona ho synaptic plasticity le mohopolo, ho fana ka bopaki bo matla bakeng sa neurotoxicity ea Aβ 1-42 oligomers.
Ho phaella moo, Su et al.(Molecular & Cellular Toxicology, 2019) e entse tlhahlobo ea transcriptomics le proteomics ea Aβ 1-42-induced neurotoxicity ho SH-SY5Y neuroblastoma lisele.Ba ile ba khetholla liphatsa tsa lefutso le liprotheine tse 'maloa tse anngoeng ke Aβ 1-42 litseleng tse amanang le mokhoa oa apoptotic, phetolelo ea protheine, mokhoa oa catabolic oa cAMP le karabelo ea khatello ea kelello ea endoplasmic reticulum.Takeda et al.(Biological Trace Element Research, 2020) e ile ea etsa lipatlisiso ka karolo ea extracellular Zn2+ ho Aβ 1-42-induced neurotoxicity ho lefu la Alzheimer.Ba bontšitse hore chefo ea Aβ 1-42 e entsoeng ka intracellular Zn2 + e ile ea potlakisa botsofali ka lebaka la keketseho e amanang le lilemo ho extracellular Zn2 +.Ba khothalelitse hore Aβ 1-42 e patiloeng khafetsa ho tsoa litsing tsa neuron e baka ho fokotseha ho amanang le lilemo le neurodegeneration ka intracellular Zn2+ dysregulation.Liphuputso tsena li fana ka maikutlo a hore Aβ 1-42 ke ntlha ea bohlokoa ho loants'a neurotoxicity le tsoelo-pele ea mafu ho lefu la Alzheimer ka ho ama mekhoa e fapaneng ea limolek'hule le liseleng bokong.
2. Tšebetso ea lithibela-mafu: Aβ 1-42 e tlalehiloe e na le ts'ebetso ea antimicrobial khahlano le likokoana-hloko tse fapaneng, joalo ka libaktheria, li-fungus le livaerase.Aβ 1-42 e ka tlama le ho senya lera la lisele tsa likokoana-hloko, e leng se lebisang ho lysis le lefu la tsona.Aβ 1-42 e ka boela ea kenya tšebetsong sesole sa 'mele sa tlhaho le ho bokella lisele tsa ho ruruha sebakeng sa ts'oaetso.Liphuputso tse ling li bontšitse hore ho bokellana ha Aβ bokong e ka 'na ea e-ba karabelo e sireletsang mafung a sa foleng kapa likotsi.Leha ho le joalo, tlhahiso e fetelletseng kapa e sa laoleheng ea Aβ le eona e ka baka ts'enyehelo ea litlamorao ho lisele tse amohelang le lisele.
Aβ 1-42 e tlalehiloe hore e bonts'a ts'ebetso ea antimicrobial khahlano le mefuta e mengata ea likokoana-hloko, joalo ka libaktheria, li-fungus le livaerase, joalo ka Staphylococcus aureus, Escherichia coli, Candida albicans, le Herpes simplex virus mofuta oa 1, ka ho sebelisana le lera la bona le. ho baka tshitiso le lysis ya bona.Kumar et al.(Journal of Alzheimer's Disease, 2016) e bontšitse phello ena ka ho bontša hore Aβ 1-42 e fetotse lera la permeability le morphology ea lisele tsa likokoana-hloko, tse lebisang lefung la bona.Ntle le ts'ebetso ea eona e tobileng ea antimicrobial, Aβ 1-42 e ka boela ea fetola karabelo ea tlhaho ea 'mele ea ho itšireletsa mafung le ho bokella lisele tsa ho ruruha sebakeng sa tšoaetso.Soscia et al.(PLoS One, 2010) e senotse karolo ena ka ho tlaleha hore Aβ 1-42 e khothalelitse tlhahiso ea li-cytokine tse pro-inflammatory le chemokine, tse kang interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte. chemoattractant protein-1 (MCP-1), le macrophage inflammatory protein-1 alpha (MIP-1α), ka microglia le astrocyte, lisele tse ka sehloohong tsa 'mele oa ho itšireletsa mafung bokong.
Setšoantšo sa 2. Li-peptide tsa Aβ li na le ts'ebetso ea antimicrobial.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's-associated amyloid beta-protein ke antimicrobial peptide. PLoS One. 2010 Mar 3;5(3):e9505.)
Le hoja liphuputso tse ling li bontšitse hore ho bokellana ha Aβ bokong e ka 'na ea e-ba karabelo e sireletsang ho mafu a sa foleng kapa likotsi, kaha Aβ e ka sebetsa e le antimicrobial peptide (AMP) le ho felisa likokoana-hloko tse ka' nang tsa e-ba teng, tšebelisano e rarahaneng pakeng tsa Aβ le likokoana-hloko e ntse e le eona. sehlooho sa lipatlisiso.Tekanyo e bobebe e totobatsoa ke lipatlisiso tsa Moir et al.(Journal of Alzheimer's Disease, 2018), e fanang ka maikutlo a hore tlhahiso e sa leka-lekaneng kapa e fetelletseng ea Aβ e ka lematsa lisele le lisele tse amohelang batho ka boomo, e bonts'a likarolo tse peli tse rarahaneng tsa likarolo tsa Aβ ho ts'oaetso le ho senyeha ha methapo.Tlhahiso e feteletseng kapa e sa laoleheng ea Aβ e ka lebisa ho kopanngoeng le ho behoa ha eona bokong, ho etsa li-oligomers tse chefo le li-fibrils tse sitisang tšebetso ea neuronal le ho baka neuroinflammation.Ts'ebetso tsena tsa pathological li amahanngoa le ho fokotseha ha kelello le ho lahleheloa ke mohopolo ho lefu la Alzheimer, lefu la neurodegenerative le khetholloang ke 'dementia' e tsoelang pele.Ka hona, tekano lipakeng tsa litlamorao tse molemo le tse kotsi tsa Aβ e bohlokoa bakeng sa ho boloka bophelo bo botle ba boko le ho thibela ho senyeha ha methapo ea kutlo.
3.Thepa ea tšepe: Aβ 1-42 e bonts'itsoe e kenya letsoho taolong ea iron homeostasis bokong.Iron ke ntho ea bohlokoa bakeng sa lits'ebetso tse ngata tsa tlhaho, empa tšepe e feteletseng e ka baka khatello ea oxidative le neurodegeneration.Aβ 1-42 e ka tlama ho tšepe 'me ea nolofatsa ho romelloa ha eona ho tsoa ho li-neuron ka ferroportin, transmembrane iron transporter.Sena se ka thusa ho thibela ho bokellana ha tšepe le chefo bokong, kaha tšepe e feteletseng e ka baka khatello ea oxidative le neurodegeneration.Duce et al.(Cell, 2010) e tlalehile hore Aβ 1-42 e tlameletsoe ho ferroportin mme e ekelitse polelo le ts'ebetso ea eona ho li-neurone, e lebisang ho fokotseng maemo a tšepe a intracellular.Ba boetse ba bonts'a hore Aβ 1-42 e fokolitse polelo ea hepcidin, hormone e thibelang ferroportin, ho li-astrocytes, ho tsoela pele ho ntlafatsa thepa ea tšepe e tsoang ho li-neurone.Leha ho le joalo, Aβ e tlanngoeng ka tšepe e ka boela ea tloaeleha ho kopanngoa le ho behoa sebakeng sa extracellular, ho etsa li-amyloid plaques.Ayton le ba bang.(Journal of Biological Chemistry, 2015) e tlaleha hore tšepe e khothalelitse ho thehoa ha li-oligomers tsa Aβ le fibrils in vitro le in vivo.Ba boetse ba bonts'a hore chelation ea tšepe e fokolitse Aβ aggregation le ho beha litoeba tsa transgenic.Ka hona, tekatekano lipakeng tsa litlamorao tse molemo le tse kotsi tsa Aβ 1-42 ho iron homeostasis e bohlokoa bakeng sa ho boloka bophelo bo botle ba boko le ho thibela neurodegeneration.
Re baetsi ba polypeptide Chaena, ba nang le phihlelo ea lilemo tse 'maloa tlhahiso ea polypeptide.Hangzhou Taijia Biotech Co., Ltd. ke moetsi oa thepa e tala ea polypeptide, e ka fanang ka mashome a likete a lisebelisoa tse tala tsa polypeptide hape e ka etsoa ho latela litlhoko.Boleng ba lihlahisoa tsa polypeptide bo botle haholo, 'me bohloeki bo ka fihla ho 98%, e' nileng ea hlokomeloa ke basebelisi lefatšeng lohle.
