Tib neeg beta-amyloid (1-42) protein, tseem hu ua Aβ 1-42, yog qhov tseem ceeb hauv kev qhib qhov paub tsis meej ntawm Alzheimer's disease.Cov peptide no ua lub luag haujlwm tseem ceeb hauv kev tsim cov amyloid plaques, pawg enigmatic uas ua rau lub hlwb ntawm Alzheimer's cov neeg mob.Nrog rau kev puas tsuaj, nws cuam tshuam kev sib txuas lus neuronal, ua rau mob, thiab induces neurotoxicity, ua rau kev txawj ntse thiab kev puas hlwb.Kev tshawb xyuas nws cov kev sib sau ua ke thiab cov tshuaj lom neeg tsis yog qhov tseem ceeb xwb;Nws yog txoj kev zoo siab mus rau kev daws Alzheimer's puzzle thiab txhim kho kev kho mob yav tom ntej.
Aβ 1-42 yog peptide fragment ntawm 42 amino acids uas yog muab los ntawm qhov cleavage ntawm amyloid precursor protein (APP) los ntawm β- thiab γ-secretases.Aβ 1-42 yog ib qho ntawm cov khoom tseem ceeb ntawm cov amyloid plaques uas nyob rau hauv lub hlwb ntawm cov neeg mob Alzheimer's disease, ib tug neurodegenerative teeb meem tshwm sim los ntawm kev txawj ntse thiab tsis nco qab.Aβ 1-42 tau pom tias muaj ntau yam haujlwm thiab kev siv hauv kev tshawb fawb txog roj ntsha thiab biomedical, xws li:
1.Neurotoxicity: Aβ 1-42 tuaj yeem tsim cov oligomers soluble uas muaj peev xwm khi rau thiab cuam tshuam kev ua haujlwm ntawm cov paj hlwb, receptors, thiab synapses.Cov oligomers no tuaj yeem ua rau oxidative kev nyuaj siab, o, thiab apoptosis hauv neurons, ua rau synaptic poob thiab neuronal tuag.Aβ 1-42 oligomers raug suav hais tias yog neurotoxic ntau dua li lwm hom Aβ, xws li Aβ 1-40, uas yog hom Aβ ntau tshaj plaws hauv lub hlwb.Aβ 1-42 oligomers kuj xav tias muaj peev xwm nthuav tawm ntawm lub xov tooj mus rau ntawm tes, zoo ib yam li prions, thiab ua rau lub misfolding thiab sib sau ua ke ntawm lwm cov proteins, xws li tau, uas ua rau neurofibrillary tangles hauv Alzheimer's kab mob.
Aβ 1-42 yog dav suav hais tias yog Aβ isoform nrog lub siab tshaj plaws neurotoxicity.Ntau cov kev tshawb fawb sim tau pom tias muaj cov kab mob neurotoxicity ntawm Aβ 1-42 siv ntau txoj kev thiab cov qauv.Piv txwv li, Lesné et al.(Lub hlwb, 2013) tshawb xyuas qhov tsim thiab toxicity ntawm Aβ oligomers, uas yog soluble aggregates ntawm Aβ monomers, thiab pom tias Aβ 1-42 oligomers muaj zog ua rau muaj kev puas tsuaj rau neuronal synapses, ua rau kev txawj ntse poob thiab neuronal poob.Lambert et al.(Kev Ua Haujlwm ntawm National Academy of Sciences, 1998) tau hais txog cov neurotoxicity ntawm Aβ 1-42 oligomers thiab pom tias lawv muaj cov tshuaj lom neeg muaj zog rau lub hauv nruab nrab lub paj hlwb, tej zaum los ntawm kev cuam tshuam cov synapses thiab neurotransmitters.Walsh et al.(Nature, 2002) tau pom cov nyhuv inhibitory ntawm Aβ 1-42 oligomers ntawm hippocampal long-term potentiation (LTP) hauv vivo, uas yog lub cellular mechanism ntawm kev kawm thiab nco.Qhov kev txwv no tau cuam tshuam nrog kev nco thiab kev kawm tsis zoo, hais txog qhov cuam tshuam ntawm Aβ 1-42 oligomers ntawm synaptic plasticity.Shankar et al.(Nature Medicine, 2008) cais Aβ 1-42 dimers ncaj qha los ntawm Alzheimer lub hlwb thiab qhia lawv cov nyhuv ntawm synaptic plasticity thiab nco, muab pov thawj empirical rau neurotoxicity ntawm Aβ 1-42 oligomers.
Tsis tas li ntawd, Su et al.(Molecular & Cellular Toxicology, 2019) ua transcriptomics thiab proteomics tsom xam ntawm Aβ 1-42-induced neurotoxicity hauv SH-SY5Y neuroblastoma hlwb.Lawv tau txheeb xyuas ntau cov noob caj noob ces thiab cov proteins uas tau cuam tshuam los ntawm Aβ 1-42 hauv txoj hauv kev uas muaj feem xyuam rau cov txheej txheem apoptotic, kev txhais cov protein, cov txheej txheem cAMP catabolic thiab cov lus teb rau endoplasmic reticulum stress.Takeda et al.(Biological Trace Element Research, 2020) tshawb xyuas lub luag haujlwm ntawm extracellular Zn2+ hauv Aβ 1-42-induced neurotoxicity hauv Alzheimer's disease.Lawv tau pom tias Aβ 1-42-induced intracellular Zn2+ toxicity tau nrawm nrog kev laus vim tias muaj hnub nyoog txog kev nce hauv extracellular Zn2+.Lawv tau hais tias Aβ 1-42 secreted tsis tu ncua los ntawm neuron terminals ua rau muaj hnub nyoog txog kev txawj ntse poob thiab neurodegeneration ntawm intracellular Zn2+ dysregulation.Cov kev tshawb fawb no qhia tias Aβ 1-42 yog qhov tseem ceeb hauv kev kho cov kab mob neurotoxicity thiab kab mob kev loj hlob hauv Alzheimer's kab mob los ntawm kev cuam tshuam ntau yam molecular thiab cellular txheej txheem hauv lub hlwb.
2. Antimicrobial kev ua: Aβ 1-42 tau tshaj tawm tias muaj cov tshuaj tiv thaiv kab mob tiv thaiv ntau yam kab mob, xws li kab mob, fungi, thiab kab mob.Aβ 1-42 tuaj yeem khi rau thiab cuam tshuam cov membranes ntawm microbial hlwb, ua rau lawv cov lysis thiab tuag.Aβ 1-42 tseem tuaj yeem qhib lub cev tiv thaiv kab mob hauv lub cev thiab nrhiav cov kab mob inflammatory mus rau qhov chaw kis kab mob.Qee qhov kev tshawb fawb tau qhia tias qhov sib txuam ntawm Aβ hauv lub hlwb yuav yog ib qho kev tiv thaiv tiv thaiv kab mob los yog raug mob.Txawm li cas los xij, ntau dhau los yog tsis muaj kev tswj hwm ntawm Aβ kuj tseem tuaj yeem ua rau muaj kev puas tsuaj rau cov tswv tsev thiab cov ntaub so ntswg.
Aβ 1-42 tau tshaj tawm tias muaj cov tshuaj tua kab mob tiv thaiv ntau yam kab mob, xws li cov kab mob, cov kab mob, thiab cov kab mob, xws li Staphylococcus aureus, Escherichia coli, Candida albicans, thiab Herpes simplex virus type 1, los ntawm kev cuam tshuam nrog lawv daim nyias nyias thiab ua rau lawv cuam tshuam thiab lysis.Kumar et al.(Journal of Alzheimer's Disease, 2016) qhia tau hais tias cov nyhuv no los ntawm kev qhia tias Aβ 1-42 hloov cov membrane permeability thiab morphology ntawm microbial hlwb, ua rau lawv tuag.Ntxiv rau nws cov tshuaj tiv thaiv kab mob ncaj qha, Aβ 1-42 tuaj yeem hloov kho lub cev tiv thaiv kab mob hauv lub cev thiab nrhiav cov kab mob inflammatory mus rau qhov chaw kis kab mob.Soscia et al.(PLoS Ib, 2010) qhia lub luag haujlwm no los ntawm kev tshaj tawm tias Aβ 1-42 txhawb kev tsim cov cytokines thiab chemokines, xws li interleukin-6 (IL-6), qog necrosis factor-alpha (TNF-α), monocyte. chemoattractant protein-1 (MCP-1), thiab macrophage inflammatory protein-1 alpha (MIP-1α), nyob rau hauv microglia thiab astrocytes, lub ntsiab tiv thaiv kab mob hauv lub hlwb.
Daim duab 2. Aβ peptides muaj cov tshuaj tiv thaiv kab mob.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS Ib . 2010 Mar 3;5(3):e9505.)
Txawm hais tias qee qhov kev tshawb fawb tau qhia tias kev sib sau ntawm Aβ hauv lub hlwb tuaj yeem yog cov lus teb rau kev tiv thaiv kab mob los yog raug mob, vim Aβ tuaj yeem ua raws li cov tshuaj tiv thaiv kab mob peptide (AMP) thiab tshem tawm cov kab mob uas muaj peev xwm, kev sib cuam tshuam ntawm Aβ thiab microbial cov ntsiab lus tseem nyob ib puag ncig. lub ntsiab lus ntawm kev tshawb nrhiav.Qhov sib npaug me me yog qhia los ntawm kev tshawb fawb ntawm Moir li al.(Journal of Alzheimer's Disease, 2018), uas qhia tias qhov tsis txaus siab lossis ntau dhau ntawm Aβ ntau lawm yuav ua rau tsis muaj peev xwm ua rau cov hlwb thiab cov ntaub so ntswg, qhia txog qhov sib txawv ntawm ob qho xwm txheej ntawm Aβ lub luag haujlwm hauv kev kis kab mob thiab neurodegeneration.Kev tsim tawm ntau dhau lossis ua tsis zoo ntawm Aβ tuaj yeem ua rau nws qhov sib sau ua ke thiab tso tawm hauv lub hlwb, tsim cov tshuaj lom oligomers thiab fibrils uas cuam tshuam rau kev ua haujlwm ntawm lub paj hlwb thiab ua rau muaj kev mob hlwb.Cov txheej txheem pathological no cuam tshuam nrog kev paub txog kev poob qis thiab kev nco poob hauv Alzheimer's kab mob, ib qho kev puas siab puas ntsws neurodegenerative yam ntxwv los ntawm kev loj hlob dementia.Yog li ntawd, qhov sib npaug ntawm cov txiaj ntsig thiab kev puas tsuaj ntawm Aβ yog qhov tseem ceeb rau kev tswj lub hlwb kev noj qab haus huv thiab tiv thaiv neurodegeneration.
3. Hlau export: Aβ 1-42 tau pom tias muaj kev koom tes hauv kev tswj hwm ntawm cov hlau homeostasis hauv lub hlwb.Hlau yog ib qho tseem ceeb ntawm ntau cov txheej txheem lom neeg, tab sis cov hlau ntau dhau tuaj yeem ua rau oxidative kev nyuaj siab thiab neurodegeneration.Aβ 1-42 tuaj yeem khi rau hlau thiab pab txhawb nws cov khoom xa tawm los ntawm cov neurons ntawm ferroportin, transmembrane hlau thauj.Qhov no tuaj yeem pab tiv thaiv kev sib sau hlau thiab tshuaj lom hauv lub hlwb, vim tias cov hlau ntau dhau tuaj yeem ua rau oxidative kev nyuaj siab thiab neurodegeneration.Duce et al.(Cell, 2010) tau tshaj tawm tias Aβ 1-42 khi rau ferroportin thiab nce nws cov kev qhia thiab kev ua haujlwm hauv cov neurons, ua rau txo qis cov hlau hauv cov cell.Lawv kuj tau pom tias Aβ 1-42 txo qis kev qhia ntawm hepcidin, ib yam tshuaj uas inhibits ferroportin, hauv astrocytes, ntxiv dag zog rau cov hlau xa tawm los ntawm cov neurons.Txawm li cas los xij, hlau-bound Aβ kuj tseem tuaj yeem ua rau muaj kev sib sau ua ke thiab tso tawm hauv qhov chaw ntxiv, tsim cov amyloid plaques.Ayton et al.(Journal of Biological Chemistry, 2015) qhia tias hlau txhawb kev tsim ntawm Aβ oligomers thiab fibrils hauv vitro thiab hauv vivo.Lawv kuj pom tau hais tias hlau chelation txo Aβ aggregation thiab deposition nyob rau hauv transgenic nas.Yog li ntawd, qhov sib npaug ntawm cov txiaj ntsig thiab kev puas tsuaj ntawm Aβ 1-42 ntawm cov hlau homeostasis yog qhov tseem ceeb rau kev tswj lub hlwb kev noj qab haus huv thiab tiv thaiv neurodegeneration.
Peb yog cov chaw tsim khoom polypeptide hauv Suav teb, nrog ntau xyoo ntawm kev paub tab hauv kev tsim cov polypeptide.Hangzhou Taijia Biotech Co., Ltd. yog lub chaw tsim khoom ntawm polypeptide raw khoom, uas tuaj yeem muab tau kaum tawm txhiab tus polypeptide raw cov ntaub ntawv thiab tuaj yeem kho raws li kev xav tau.Qhov zoo ntawm cov khoom polypeptide yog qhov zoo heev, thiab qhov purity tuaj yeem ncav cuag 98%, uas tau lees paub los ntawm cov neeg siv thoob plaws ntiaj teb. Zoo siab txais tos los tham nrog peb.
