Beta-amyloid na ɗan adam (1-42), wanda kuma aka sani da Aβ 1-42, shine maɓalli mai mahimmanci don buɗe asirin cutar Alzheimer.Wannan peptide yana taka muhimmiyar rawa wajen samar da amyloid plaques, gungu masu ban mamaki waɗanda ke lalata kwakwalwar masu cutar Alzheimer.Tare da sakamako mai lalacewa, yana lalata sadarwar neuronal, yana haifar da kumburi, kuma yana haifar da neurotoxicity, yana haifar da rashin fahimta da lalacewar jijiyoyi.Bincika yadda ake tattara ta da kuma hanyoyin guba ba kawai mahimmanci ba ne;tafiya ce mai ban sha'awa zuwa warware wuyar warwarewar Alzheimer da haɓaka hanyoyin kwantar da hankali na gaba.
Aβ 1-42 guntun peptide ne na amino acid 42 wanda aka samo daga ɓarkewar furotin precursor (APP) ta β- da γ-asiri.Aβ 1-42 yana daya daga cikin manyan abubuwan da ke tattare da amyloid plaques da ke taruwa a cikin kwakwalwar marasa lafiya da cutar Alzheimer, rashin lafiyar neurodegenerative wanda ke da rashin fahimta da kuma asarar ƙwaƙwalwar ajiya.An nuna Aβ 1-42 yana da ayyuka daban-daban da aikace-aikace a cikin binciken ilimin halitta da na halitta, kamar:
1. Neurotoxicity: Aβ 1-42 na iya samar da oligomers masu narkewa waɗanda ke da ikon ɗaure da rushe aikin membranes neuronal, masu karɓa, da synapses.Wadannan oligomers kuma na iya haifar da danniya na oxidative, kumburi, da apoptosis a cikin ƙananan ƙwayoyin cuta, wanda ke haifar da asarar synaptic da mutuwar neuronal.Aβ 1-42 oligomers ana daukar su mafi neurotoxic fiye da sauran nau'ikan Aβ, kamar Aβ 1-40, wanda shine mafi yawan nau'in Aβ a cikin kwakwalwa.Aβ 1-42 oligomers kuma ana tsammanin za su iya yaduwa daga tantanin halitta zuwa tantanin halitta, kama da prions, kuma suna haifar da ɓarna da haɗuwa da wasu sunadaran, irin su tau, wanda ke haifar da tangles neurofibrillary a cikin cutar Alzheimer.
Aβ 1-42 ana ɗaukarsa ko'ina azaman Aβ isoform tare da mafi girman neurotoxicity.Yawancin nazarin gwaji sun nuna neurotoxicity na Aβ 1-42 ta amfani da hanyoyi da samfurori daban-daban.Alal misali, Lesné et al.(Brain, 2013) yayi bincike akan samuwar da kuma guba na Aβ oligomers, wadanda sune masu narkewa na Aβ monomers, kuma sun nuna cewa Aβ 1-42 oligomers yana da tasiri mai tasiri akan synapses na neuronal, wanda ke haifar da raguwar hankali da asarar neuronal.Lambert et al.(Ayyukan ci gaba na Kwalejin Kimiyya na Kasa, 1998) ya nuna alamar neurotoxicity na Aβ 1-42 oligomers kuma sun gano cewa suna da tasiri mai guba a kan tsarin kulawa na tsakiya, mai yiwuwa ta hanyar rinjayar synapses da neurotransmitters.Walsh et al.(Nature, 2002) ya nuna tasirin hanawa na Aβ 1-42 oligomers akan ƙarfin ƙarfin lokaci na hippocampal (LTP) a cikin vivo, wanda shine tsarin salon salula wanda ke ƙarƙashin koyo da ƙwaƙwalwa.Wannan hanawa yana hade da ƙwaƙwalwar ajiya da rashin ilmantarwa, yana jaddada tasirin Aβ 1-42 oligomer akan filastik synaptic.Shankar et al.(Nature Medicine, 2008) ware Aβ 1-42 dimers kai tsaye daga kwakwalwar Alzheimer kuma sun nuna tasirin su akan filastik synaptic da ƙwaƙwalwar ajiya, suna ba da shaida mai ma'ana ga neurotoxicity na Aβ 1-42 oligomers.
Bugu da kari, Su et al.(Molecular & Cellular Toxicology, 2019) sun yi fassarar fassarar da nazarin proteomics na Aβ 1-42-induced neurotoxicity a cikin sel SH-SY5Y neuroblastoma.Sun gano yawancin kwayoyin halitta da sunadaran da Aβ 1-42 suka shafa a cikin hanyoyin da suka shafi tsarin apoptotic, fassarar furotin, tsarin catabolic na CAMP da amsawa ga damuwa na endoplasmic reticulum.Takeda et al.(Biological Trace Element Research, 2020) yayi bincike game da rawar da Zn2+ ke ciki a cikin Aβ 1-42-induced neurotoxicity a cikin cutar Alzheimer.Sun nuna cewa Aβ 1-42-induced intracellular Zn2+ mai guba yana haɓaka tare da tsufa saboda haɓakar shekaru da ke da alaƙa a cikin Zn2+ na waje.Sun ba da shawarar cewa Aβ 1-42 da aka ɓoye ta ci gaba daga tashoshi na neuron yana haifar da raguwar fahimi da ke da alaƙa da tsufa da haɓakar neurodegeneration ta hanyar intracellular Zn2+ dysregulation.Wadannan binciken sun nuna cewa Aβ 1-42 shine mabuɗin mahimmanci a cikin tsaka-tsaki na neurotoxicity da ci gaban cututtuka a cikin cutar Alzheimer ta hanyar tasiri daban-daban na kwayoyin halitta da tsarin salula a cikin kwakwalwa.
2. Ayyukan Antimicrobial: An ba da rahoton Aβ 1-42 yana da aikin antimicrobial akan ƙwayoyin cuta daban-daban, kamar ƙwayoyin cuta, fungi, da ƙwayoyin cuta.Aβ 1-42 na iya ɗaure da rushe membranes na ƙananan ƙwayoyin cuta, wanda ke haifar da lysis da mutuwa.Aβ 1-42 kuma na iya kunna tsarin rigakafi na asali da kuma ɗaukar ƙwayoyin kumburi zuwa wurin kamuwa da cuta.Wasu nazarin sun nuna cewa tarawar Aβ a cikin kwakwalwa na iya zama amsawar kariya ga cututtuka ko raunin da ya faru.Koyaya, haɓakar Aβ da yawa ko rashin tsari na iya haifar da lahani ga sel da kyallen takarda.
An ba da rahoton Aβ 1-42 don nuna ayyukan antimicrobial akan nau'ikan ƙwayoyin cuta, irin su ƙwayoyin cuta, fungi, da ƙwayoyin cuta, irin su Staphylococcus aureus, Escherichia coli, Candida albicans, da Herpes simplex virus type 1, ta hanyar yin hulɗa tare da membranes da su. haifar da rushewar su da lysis.Kumar et al.(Journal of Alzheimer's Disease, 2016) ya nuna wannan sakamako ta hanyar nuna cewa Aβ 1-42 ya canza canjin membrane da ilimin halittar jikin kwayoyin halitta, wanda ya kai ga mutuwarsu.Bugu da ƙari ga aikin maganin ƙwayoyin cuta kai tsaye, Aβ 1-42 kuma na iya canza yanayin amsawar rigakafi da kuma ɗaukar ƙwayoyin kumburi zuwa wurin kamuwa da cuta.Soscia et al.(PLoS One, 2010) ya bayyana wannan rawar ta hanyar bayar da rahoto cewa Aβ 1-42 ya ƙarfafa samar da cytokines masu kumburi da chemokines, irin su interleukin-6 (IL-6), ƙwayar necrosis factor-alpha (TNF-α), monocyte. chemoattractant protein-1 (MCP-1), da macrophage inflammatory protein-1 alpha (MIP-1α), a cikin microglia da astrocytes, babban kwayoyin rigakafi a cikin kwakwalwa.
Hoto 2. Aβ peptides suna da aikin 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 da ke da alaƙa da cutar Alzheimer shine peptide antimicrobial. PLoS One . 2010 Maris 3; 5 (3): e9505.)
Duk da yake wasu nazarin sun nuna cewa tarawar Aβ a cikin kwakwalwa na iya zama amsawar kariya ga cututtuka na kullum ko raunin da ya faru, kamar yadda Aβ zai iya aiki a matsayin peptide antimicrobial (AMP) da kuma kawar da cututtuka masu haɗari, hadaddun hulɗar tsakanin Aβ da microbial abubuwa sun kasance batun bincike.Ana nuna ma'auni mai laushi ta hanyar bincike na Moir et al.(Journal of Alzheimer's Disease, 2018), wanda ke nuna cewa rashin daidaituwa ko wuce kima samar da Aβ na iya cutar da kwayoyin halitta da kyallen takarda ba da gangan ba, yana nuna yanayin dual dual na ayyukan Aβ a cikin kamuwa da cuta da neurodegeneration.Ƙarfafawa ko rashin daidaituwa na Aβ na iya haifar da haɗuwa da ƙaddamarwa a cikin kwakwalwa, samar da oligomers masu guba da fibrils waɗanda ke lalata aikin neuronal kuma suna haifar da neuroinflammation.Wadannan matakai na pathological suna da alaƙa da raguwar fahimi da asarar ƙwaƙwalwar ajiya a cikin cutar Alzheimer, rashin lafiyar neurodegenerative wanda ke da ciwon ci gaba.Sabili da haka, ma'auni tsakanin tasiri mai amfani da lalacewa na Aβ yana da mahimmanci don kiyaye lafiyar kwakwalwa da kuma hana neurodegeneration.
3. Iron fitarwa: An nuna Aβ 1-42 yana da hannu a cikin ka'idar homeostasis na ƙarfe a cikin kwakwalwa.Iron yana da mahimmanci ga yawancin hanyoyin nazarin halittu, amma wuce haddi na ƙarfe kuma yana iya haifar da damuwa na iskar oxygen da neurodegeneration.Aβ 1-42 na iya ɗaure baƙin ƙarfe kuma sauƙaƙe fitar da shi daga neurons ta hanyar ferroportin, mai jigilar ƙarfe na transmembrane.Wannan na iya taimakawa wajen hana tarawar ƙarfe da guba a cikin kwakwalwa, kamar yadda baƙin ƙarfe ya wuce kima zai iya haifar da damuwa na oxidative da neurodegeneration.Duce et al.(Cell, 2010) ya ruwaito cewa Aβ 1-42 yana ɗaure zuwa ferroportin kuma yana ƙara yawan magana da aiki a cikin ƙwayoyin cuta, wanda ke haifar da rage matakan ƙarfe na ciki.Sun kuma nuna cewa Aβ 1-42 ya rage bayyanar hepcidin, hormone wanda ke hana ferroportin, a cikin astrocytes, yana ƙara haɓaka fitar da baƙin ƙarfe daga ƙananan ƙwayoyin cuta.Koyaya, Aβ mai ɗaure baƙin ƙarfe na iya zama mai saurin haɗuwa da sakawa a cikin sararin samaniya, ƙirƙirar plaques amyloid.Ayton et al.(Journal of Biological Chemistry, 2015) ya ruwaito cewa ƙarfe ya inganta samuwar Aβ oligomers da fibrils a cikin vitro da in vivo.Har ila yau, sun nuna cewa chelation na baƙin ƙarfe ya rage yawan Aβ da kuma sakawa a cikin mice transgenic.Sabili da haka, ma'auni tsakanin fa'idodin amfani da lahani na Aβ 1-42 akan homeostasis na ƙarfe yana da mahimmanci don kiyaye lafiyar kwakwalwa da hana haɓakar neurodegeneration.
Mu masu sana'a ne na polypeptide a kasar Sin, tare da shekaru masu yawa na kwarewa a cikin samar da polypeptide.Hangzhou Taijia Biotech Co., Ltd. ƙwararren ƙwararren masana'anta ne na polypeptide, wanda zai iya samar da dubun dubatan polypeptide albarkatun ƙasa kuma ana iya keɓance shi gwargwadon buƙatu.Ingancin samfuran polypeptide yana da kyau sosai, kuma tsabta zai iya kaiwa 98%, wanda masu amfani suka gane a duk faɗin duniya. Barka da tuntuɓar mu.
