Protein beta-amyloid (1-42), nke a makwaara dị ka Aβ 1-42, bụ isi ihe na-emepe ihe omimi nke ọrịa Alzheimer.Nke a peptide na-ekere òkè bụ isi n'ịmepụta amyloid plaques, ụyọkọ enigmatic na-emebi ụbụrụ ndị ọrịa Alzheimer.Site na mmetụta na-emebi emebi, ọ na-akpaghasị nkwurịta okwu neuronal, na-ebute mbufụt, ma na-ebute neurotoxicity, na-eduga n'inwe nghọta na mmebi akwara.Nyochaa usoro nchịkọta ya na nsí ya abụghị naanị ihe dị mkpa;ọ bụ njem na-akpali akpali iji dozie mgbagwoju anya Alzheimer na ịzụlite usoro ọgwụgwọ n'ọdịnihu.
Aβ 1-42 bụ iberi peptide nke amino acid 42 sitere na nbipu nke protein amyloid precursor (APP) site na β- na γ-secretases.Aβ 1-42 bụ otu n'ime ihe ndị bụ isi nke plaques amyloid nke na-agbakọba n'ụbụrụ ndị ọrịa nwere ọrịa Alzheimer, ọrịa neurodegenerative nke a na-eji eme ihe na-enweghị uche na nkwụsị ebe nchekwa.E gosiputara Aβ 1-42 nwere ọrụ na ngwa dị iche iche na nyocha nke ndu na biomedical, dịka:
1. Neurotoxicity: Aβ 1-42 nwere ike ịmepụta oligomer soluble nke nwere ike ijikọ na imebi ọrụ nke membranes neuronal, ndị na-anabata ya, na synapses.Ndị oligomers a nwekwara ike ịkpata nrụgide oxidative, mbufụt, na apoptosis na neurons, na-eduga na ọnwụ synapti na ọnwụ neuronal.A na-ewere oligomer Aβ 1-42 dị ka neurotoxic karịa ụdị Aβ ndị ọzọ, dị ka Aβ 1-40, nke bụ ụdị Aβ kachasị na ụbụrụ.A na-echekwa na ndị oligomers Aβ 1-42 nwere ike ịgbasa site na cell gaa na cell, dị ka prions, ma kpalite mgbaghara na nchịkọta nke protein ndị ọzọ, dị ka tau, nke na-emepụta neurofibrillary tangles na ọrịa Alzheimer.
A na-ahụta Aβ 1-42 dị ka Aβ isoform nwere neurotoxicity kachasị elu.Ọtụtụ nchọpụta nnwale egosila neurotoxicity nke Aβ 1-42 site na iji ụzọ na ụdị dị iche iche.Dịka ọmụmaatụ, Lesné et al.(Brain, 2013) nyochara nhazi na nsi nke Aβ oligomers, nke bụ nchịkọta soluble nke Aβ monomers, ma gosi na Aβ 1-42 oligomers nwere mmetụta dị njọ karị na synapses neuronal, na-eduga n'ịghọta mbelata na nkwụsị nke neuronal.Lambert et al.(Ihe omume nke National Academy of Sciences, 1998) mere ka neurotoxicity nke Aβ 1-42 oligomer pụta ìhè ma chọpụta na ha nwere mmetụta siri ike na-egbu egbu na usoro nhụjuanya nke etiti, ikekwe site na-emetụta synapses na neurotransmitters.Walsh et al.(Nature, 2002) gosipụtara mmetụta mgbochi nke Aβ 1-42 oligomers na ike ogologo oge hippocampal (LTP) na vivo, nke bụ usoro cellular na-adabere na mmụta na ebe nchekwa.Ejikọtara ihe mgbochi a na ebe nchekwa na nkwarụ mmụta, na-emesi mmetụta nke Aβ 1-42 oligomer na synaptic plasticity.Shankar et al.(Nature Medicine, 2008) dịpụrụ adịpụ Aβ 1-42 dimers kpọmkwem site na ụbụrụ Alzheimer ma gosipụta mmetụta ha na synaptic plasticity na ebe nchekwa, na-enye ihe àmà doro anya maka neurotoxicity nke Aβ 1-42 oligomers.
Na mgbakwunye, Su et al.(Molecular & Cellular Toxicology, 2019) mere transcriptomics na nyocha proteomics nke Aβ 1-42 na-akpata neurotoxicity na sel SH-SY5Y neuroblastoma.Ha chọpụtara ọtụtụ mkpụrụ ndụ ihe nketa na protein ndị Aβ 1-42 metụtara na ụzọ ndị metụtara usoro apoptotic, nsụgharị protein, cAMP catabolic usoro na nzaghachi na nrụgide endoplasmic reticulum.Takeda et al.(Nnyocha ihe omimi nke ihe omimi, 2020) nyochara ọrụ nke extracellular Zn2+ na neurotoxicity Aβ 1-42 kpatara na ọrịa Alzheimer.Ha gosiri na Aβ 1-42 na-ebute intracellular Zn2+ toxicity na-eme ka ọ dịkwuo elu site na ịka nká n'ihi mmụba metụtara afọ na extracellular Zn2+.Ha tụrụ aro na Aβ 1-42 zoro ezo na-aga n'ihu site na njedebe neuron na-akpata mbelata ọgụgụ isi metụtara afọ na neurodegeneration site na intracellular Zn2+ dysregulation.Ọmụmụ ihe ndị a na-egosi na Aβ 1-42 bụ isi ihe na-eme ka mgbasa ozi neurotoxicity na ọganihu ọrịa na ọrịa Alzheimer site na-emetụta usoro dị iche iche molecular na cellular na ụbụrụ.
2. Ọrụ mgbochi ọrịa: A kọwo na Aβ 1-42 nwere ọrụ antimicrobial megide nje dị iche iche, dị ka nje bacteria, fungi, na nje.Aβ 1-42 nwere ike jikọta ma mebie membranes nke mkpụrụ ndụ microbial, na-eduga na lysis na ọnwụ.Aβ 1-42 nwekwara ike ime ka usoro ahụ ji alụso ọrịa ọgụ pụta ma weta mkpụrụ ndụ mkpali na saịtị nke ọrịa.Ụfọdụ ọmụmụ na-atụ aro na nchịkọta Aβ na ụbụrụ nwere ike ịbụ nzaghachi nchebe maka ọrịa na-adịghị ala ala ma ọ bụ mmerụ ahụ.Otú ọ dị, mmepụta Aβ gabigara ókè ma ọ bụ nke a na-achịkwaghị achịkwa nwekwara ike ịkpata mmebi nke mkpụrụ ndụ na anụ ahụ.
A kọkwara Aβ 1-42 ka ọ gosipụta ọrụ antimicrobial megide ụdị nje dị iche iche, dị ka nje bacteria, fungi, na nje, dị ka Staphylococcus aureus, Escherichia coli, Candida albicans, na Herpes simplex virus ụdị 1, site na imekọrịta ihe na akpụkpọ ahụ ha. na-akpata ọgba aghara na lysis ha.Kumar et al.(Journal of Alzheimer's Disease, 2016) gosipụtara mmetụta a site n'igosi na Aβ 1-42 gbanwere akpụkpọ anụ ahụ na morphology nke mkpụrụ ndụ microbial, na-eduga na ọnwụ ha.Na mgbakwunye na ihe mgbochi nje ya kpọmkwem, Aβ 1-42 nwekwara ike gbanwee mmeghachi omume mgbochi ebumpụta ụwa wee weta mkpụrụ ndụ mkpali na saịtị nke ọrịa.Soscia et al.(PLoS One, 2010) kpughere ọrụ a site n'ịkọ na Aβ 1-42 kpaliri mmepụta nke cytokines pro-inflammatory na chemokines, dị ka interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte. chemoattractant protein-1 (MCP-1), na macrophage inflammatory protein-1 alpha (MIP-1α), na microglia na astrocytes, bụ isi sel na-alụso ọrịa ọgụ na ụbụrụ.
Ọgụgụ 2. Aβ peptides nwere ọrụ antimicrobial.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. Amyloid beta-protein metụtara ọrịa Alzheimer bụ peptide antimicrobial. PLoS One .2010 Maachị 3;5(3):e9505.)
Ọ bụ ezie na ụfọdụ ọmụmụ na-atụ aro na nchịkọta Aβ na ụbụrụ nwere ike ịbụ nzaghachi nchebe maka ọrịa na-adịghị ala ala ma ọ bụ mmerụ ahụ, dị ka Aβ nwere ike ime dị ka peptide antimicrobial (AMP) ma wepụ ihe ndị nwere ike ịkpata ọrịa, mgbagwoju anya n'etiti Aβ na microbial ọcha na-anọgide isiokwu nyocha.A na-egosipụta nguzozi dị nro site na nyocha nke Moir et al.(Akwụkwọ akụkọ nke Ọrịa Alzheimer, 2018), nke na-atụ aro na mmepụta Aβ ezighi ezi ma ọ bụ oke nwere ike imerụ sel na anụ ahụ ndị ọbịa n'amaghị ama, na-egosipụta ụdị mgbagwoju anya abụọ nke ọrụ Aβ na ọrịa na neurodegeneration.Mmepụta oke ma ọ bụ nke dysregulated nke Aβ nwere ike iduga mkpokọta ya na ntinye ya na ụbụrụ, na-eme oligomer na-egbu egbu na fibrils nke na-emebi ọrụ neuronal ma na-ebute neuroinflammation.Usoro ndị a na-ahụ maka ọrịa na-ejikọta ya na mbelata ọgụgụ isi na nkwụsị ebe nchekwa na ọrịa Alzheimer, ọrịa neurodegenerative nke mgbaka na-aga n'ihu.Ya mere, nguzozi n'etiti uru bara uru na mmetụta ọjọọ nke Aβ dị oké mkpa maka ịnọgide na-enwe ahụike ụbụrụ na igbochi neurodegeneration.
3.Iron mbupụ: E gosiputara Aβ 1-42 na-etinye aka na nhazi nke iron homeostasis na ụbụrụ.Ígwè bụ ihe dị mkpa maka ọtụtụ usoro ndu, mana oke ígwè nwekwara ike ịkpata nrụgide oxidative na neurodegeneration.Aβ 1-42 nwere ike jikọta na ígwè ma mee ka mbupụ ya site na neurons site na ferroportin, onye na-ebugharị ígwè transmembrane.Nke a nwere ike inye aka gbochie nchịkọta ígwè na nsị na ụbụrụ, n'ihi na oke ígwè nwere ike ịkpata nrụgide oxidative na neurodegeneration.Duce et al.(Cell, 2010) kọrọ na Aβ 1-42 na-ejikọta ferroportin ma mụbaa nkwupụta ya na ọrụ ya na neurons, na-eduga n'ịbelata ọkwa ígwè intracellular.Ha gosikwara na Aβ 1-42 belatara okwu hepcidin, homonụ nke na-egbochi ferroportin, na astrocytes, na-eme ka mbupụ ígwè si na neurons dịkwuo elu.Otú ọ dị, Aβ na-ekekọta ígwè nwekwara ike ịdị na-adịwanye mfe na nchịkọta na ntinye na oghere extracellular, na-akpụ amyloid plaques.Ayton et al.(Journal of Biological Chemistry, 2015) kọrọ na ígwè kwalitere nguzobe nke Aβ oligomers na fibrils in vitro na in vivo.Ha gosikwara na chelation ígwè na-ebelata mkpokọta Aβ na ntinye na ụmụ oke transgenic.Ya mere, nguzozi n'etiti uru bara uru na mmetụta ọjọọ nke Aβ 1-42 na iron homeostasis dị oké mkpa maka ịnọgide na-enwe ahụike ụbụrụ na igbochi neurodegeneration.
Anyị bụ ndị na-emepụta polypeptide na China, nwere ahụmahụ tozuru okè na mmepụta polypeptide ọtụtụ afọ.Hangzhou Taijia Biotech Co., Ltd bụ ọkachamara polypeptide akụrụngwa emeputa, nke nwere ike inye iri puku kwuru iri puku polypeptide akụrụngwa na nwekwara ike ahaziri dị ka mkpa.Ogo nke ngwaahịa polypeptide dị mma, ịdị ọcha nwere ike iru 98%, nke ndị ọrụ ghọtara n'ụwa niile. Nnọọ ịkpọtụrụ anyị.
