Puloteni ya beta-amyloid (1-42) yaumunthu, yomwe imadziwikanso kuti Aβ 1-42, ndi chinthu chofunikira kwambiri pakutsegula zinsinsi za matenda a Alzheimer's.Peptide iyi imagwira ntchito yofunika kwambiri popanga zolembera za amyloid, masango odabwitsa omwe amawononga ubongo wa odwala a Alzheimer's.Ndi zotsatira zowononga, zimasokoneza kulankhulana kwa minyewa, kumayambitsa kutupa, ndi kuyambitsa neurotoxicity, zomwe zimayambitsa kuwonongeka kwa chidziwitso ndi kuwonongeka kwa mitsempha.Kufufuza njira zake zophatikizira ndi kawopsedwe sikofunikira kokha;ndi ulendo wosangalatsa wofuna kuthana ndi vuto la Alzheimer's ndikukhazikitsa zithandizo zamtsogolo.
Aβ 1-42 ndi chidutswa cha peptide cha 42 amino acid chomwe chimachokera ku cleavage ya amyloid precursor protein (APP) ndi β- ndi γ-secretases.Aβ 1-42 ndi chimodzi mwa zigawo zikuluzikulu za zolembera za amyloid zomwe zimawunjikana muubongo wa odwala omwe ali ndi matenda a Alzheimer's, matenda a neurodegenerative omwe amadziwika ndi kuwonongeka kwa chidziwitso komanso kukumbukira kukumbukira.Aβ 1-42 yawonetsedwa kuti ili ndi ntchito zosiyanasiyana ndikugwiritsa ntchito pazofufuza zamankhwala ndi zamankhwala, monga:
1. Neurotoxicity: Aβ 1-42 imatha kupanga ma oligomers osungunuka omwe amatha kumangirira ndikusokoneza magwiridwe antchito a nembanemba, zolandilira, ndi ma synapses.Oligomers awa amathanso kuyambitsa kupsinjika kwa okosijeni, kutupa, ndi apoptosis mu ma neurons, zomwe zimatsogolera kutayika kwa synaptic ndi kufa kwa neuronal.Aβ 1-42 oligomers amaonedwa kuti ndi neurotoxic kwambiri kuposa mitundu ina ya Aβ, monga Aβ 1-40, yomwe ili yochuluka kwambiri ya Aβ mu ubongo.Aβ 1-42 oligomers amaganiziridwanso kuti amatha kufalikira kuchokera ku selo kupita ku selo, mofanana ndi prions, ndi kuyambitsa kusokoneza ndi kuphatikiza kwa mapuloteni ena, monga tau, omwe amapanga neurofibrillary tangles mu matenda a Alzheimer's.
Aβ 1-42 imadziwika kwambiri ngati Aβ isoform yokhala ndi neurotoxicity yayikulu kwambiri.Maphunziro angapo oyesera awonetsa neurotoxicity ya Aβ 1-42 pogwiritsa ntchito njira ndi mitundu yosiyanasiyana.Mwachitsanzo, Lesné et al.(Brain, 2013) adafufuza momwe ma oligomers a Aβ amapangidwira komanso kuwopsa kwa ma oligomers, omwe ndi magulu osungunuka a Aβ monomers, ndipo adawonetsa kuti ma oligomer a Aβ 1-42 anali ndi zotsatira zowononga kwambiri pa ma neuronal synapses, zomwe zimapangitsa kuchepa kwa chidziwitso komanso kutayika kwa neuronal.Lambert et al.(Proceedings of the National Academy of Sciences, 1998) adawonetsa za neurotoxicity ya Aβ 1-42 oligomers ndipo adapeza kuti anali ndi poizoni wakupha kwambiri pakatikati pa mitsempha ya mitsempha, mwinamwake pokhudza ma synapses ndi neurotransmitters.Walsh ndi al.(Nature, 2002) adawonetsa zoletsa za Aβ 1-42 oligomers pa hippocampal long-term potentiation (LTP) mu vivo, yomwe ndi njira yama cell yomwe imayambitsa kuphunzira ndi kukumbukira.Kulepheretsa uku kudalumikizidwa ndi vuto la kukumbukira ndi kuphunzira, kutsindika momwe ma oligomer a Aβ 1-42 pa synaptic plasticity.Shankar et al.(Nature Medicine, 2008) adapatula Aβ 1-42 dimers mwachindunji kuchokera ku ubongo wa Alzheimer's ndipo adawonetsa zotsatira zake pa synaptic plasticity ndi kukumbukira, kupereka umboni wotsimikizira za neurotoxicity ya Aβ 1-42 oligomers.
Kuphatikiza apo, Su et al.(Molecular & Cellular Toxicology, 2019) anachita transcriptomics and proteomics analysis of Aβ 1-42-induced neurotoxicity mu SH-SY5Y neuroblastoma cells.Iwo adazindikira majini angapo ndi mapuloteni omwe adakhudzidwa ndi Aβ 1-42 munjira zokhudzana ndi njira ya apoptotic, kumasulira kwa mapuloteni, njira ya catabolic ya cAMP komanso kuyankha kupsinjika kwa endoplasmic reticulum.Takeda et al.(Biological Trace Element Research, 2020) idafufuza momwe Zn2+ yowonjezera imathandizira mu Aβ 1-42-induced neurotoxicity mu matenda a Alzheimer's.Iwo adawonetsa kuti Aβ 1-42-induced intracellular Zn2 + toxicity inafulumizitsidwa ndi ukalamba chifukwa cha kuwonjezeka kwa zaka za extracellular Zn2 +.Ananenanso kuti Aβ 1-42 yobisidwa mosalekeza kuchokera ku ma neuron terminals imayambitsa kuchepa kwa chidziwitso chokhudzana ndi ukalamba komanso kusokonezeka kwa neurodegeneration kudzera mu intracellular Zn2+ dysregulation.Kafukufukuyu akuwonetsa kuti Aβ 1-42 ndiye chinthu chofunikira kwambiri pakuyanjanitsa matenda a neurotoxicity komanso kupita patsogolo kwa matenda mu matenda a Alzheimer's pokhudza njira zosiyanasiyana zama cell ndi ma cell muubongo.
2. Antimicrobial ntchito: Aβ 1-42 akuti ali ndi antimicrobial zochita motsutsana ndi tizilombo tosiyanasiyana, monga mabakiteriya, mafangasi, ndi ma virus.Aβ 1-42 imatha kumangirira ndikusokoneza ma cell a ma cell, zomwe zimatsogolera ku lysis ndi kufa kwawo.Aβ 1-42 imathanso kuyambitsa chitetezo cham'thupi ndikusonkhanitsa ma cell otupa pamalo omwe ali ndi matenda.Kafukufuku wina wasonyeza kuti kudzikundikira kwa Aβ mu ubongo kungakhale njira yotetezera ku matenda aakulu kapena kuvulala.Komabe, kuchulukitsitsa kapena kusalongosoka kwa Aβ kungayambitsenso kuwonongeka kwa ma cell ndi minyewa.
Aβ 1-42 yanenedwa kuti ikuwonetsa zochita zowononga tizilombo toyambitsa matenda, monga mabakiteriya, bowa, ndi mavairasi, monga Staphylococcus aureus, Escherichia coli, Candida albicans, ndi Herpes simplex virus type 1, polumikizana ndi nembanemba yawo ndi kuchititsa kusokonezeka kwawo ndi lysis.Kumar et al.(Journal of Alzheimer's Disease, 2016) inasonyeza izi posonyeza kuti Aβ 1-42 inasintha ma membrane permeability ndi morphology ya maselo a tizilombo toyambitsa matenda, zomwe zimapangitsa kuti afe.Kuphatikiza pa zochita zake zachindunji za antimicrobial, Aβ 1-42 imathanso kuwongolera momwe chitetezo cha mthupi chimayankhira ndikulemba ma cell otupa pamalo omwe ali ndi matenda.Soscia et al.(PLoS One, 2010) adavumbulutsa ntchitoyi pofotokoza kuti Aβ 1-42 inalimbikitsa kupanga ma cytokines ndi chemokines oyambitsa kutupa, monga interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), ndi macrophage inflammatory protein-1 alpha (MIP-1α), mu microglia ndi astrocytes, maselo akuluakulu a chitetezo cha mthupi mu ubongo.
Chithunzi 2. Aβ peptides ali ndi antimicrobial zochita.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. Matenda a Alzheimer's amyloid beta-protein ndi antimicrobial peptide. PLoS One . 2010 Mar 3;5(3):e9505.)
Ngakhale kuti kafukufuku wina wasonyeza kuti kudzikundikira kwa Aβ mu ubongo kungakhale njira yotetezera ku matenda aakulu kapena kuvulala, monga Aβ amatha kukhala ngati antimicrobial peptide (AMP) ndikuchotsa tizilombo toyambitsa matenda, kuyanjana kovuta pakati pa Aβ ndi tizilombo toyambitsa matenda kumakhalabe. mutu wa kafukufuku.Kusacheperako kumawonetsedwa ndi kafukufuku wa Moir et al.(Journal of Alzheimer's Disease, 2018), yomwe ikuwonetsa kuti kusalinganika kapena kuchulukitsitsa kwa Aβ kumatha kuvulaza ma cell ndi minyewa yomwe imachitikira, kuwonetsa zovuta zapawiri zomwe Aβ amagwira pa matenda ndi neurodegeneration.Kuchuluka kapena kusalongosoka kwa Aβ kungayambitse kuphatikizika kwake ndi kuyika kwake muubongo, kupanga oligomers oopsa ndi ma fibrils omwe amasokoneza magwiridwe antchito a neuronal ndikupangitsa neuroinflammation.Njira zamatendawa zimalumikizidwa ndi kuchepa kwachidziwitso komanso kuwonongeka kwa kukumbukira mu matenda a Alzheimer's, matenda a neurodegenerative omwe amadziwika ndi kusokonezeka kwaubongo.Chifukwa chake, kulinganiza pakati pa zopindulitsa ndi zowononga za Aβ ndikofunikira kuti ubongo ukhale wathanzi komanso kupewa kusokonezeka kwa ubongo.
3.Iron kutumiza kunja: Aβ 1-42 yawonetsedwa kuti ikukhudzidwa ndi kayendetsedwe ka iron homeostasis mu ubongo.Iron ndi chinthu chofunikira pazachilengedwe zambiri, koma chitsulo chochulukirapo chingayambitsenso kupsinjika kwa okosijeni ndi neurodegeneration.Aβ 1-42 imatha kumangirira kuchitsulo ndikuwongolera kutumiza kwake kuchokera ku ma neuron kudzera pa ferroportin, transmembrane iron transporter.Izi zitha kuthandiza kupewa kudzikundikira kwachitsulo komanso kawopsedwe muubongo, chifukwa chitsulo chochulukirapo chingayambitse kupsinjika kwa okosijeni ndi neurodegeneration.Duce et al.(Cell, 2010) inanena kuti Aβ 1-42 imamangiriridwa ku ferroportin ndikuwonjezera mawonekedwe ake ndi zochita zake mu ma neuron, zomwe zimapangitsa kuchepa kwachitsulo chachitsulo.Adawonetsanso kuti Aβ 1-42 idachepetsa mawu a hepcidin, mahomoni omwe amaletsa ferroportin, mu astrocytes, kupititsa patsogolo kutulutsa kwachitsulo kuchokera ku ma neuron.Komabe, Aβ yomangidwa ndi chitsulo ingakhalenso yowonjezereka ndikuyika mu malo a extracellular, kupanga ma amyloid plaques.Ayton ndi al.(Journal of Biological Chemistry, 2015) inanena kuti chitsulo chinalimbikitsa kupanga Aβ oligomers ndi fibrils mu vitro ndi mu vivo.Adawonetsanso kuti chitsulo chelation chimachepetsa kuphatikizika kwa Aβ ndikuyika mu mbewa za transgenic.Chifukwa chake, kulinganiza pakati pa zopindulitsa komanso zowononga za Aβ 1-42 pa iron homeostasis ndikofunikira kuti ubongo ukhale wathanzi komanso kupewa kusokonezeka kwa ma neurodegeneration.
Ndife opanga ma polypeptide ku China, omwe ali ndi zaka zingapo okhwima pakupanga polypeptide.Hangzhou Taijia Biotech Co., Ltd. ndi katswiri wopanga polypeptide yaiwisi, yomwe imatha kupereka makumi masauzande azinthu zopangira polypeptide ndipo imathanso kusinthidwa malinga ndi zosowa.Ubwino wa zinthu za polypeptide ndi zabwino kwambiri, ndipo chiyero chimatha kufika 98%, chomwe chadziwika ndi ogwiritsa ntchito padziko lonse lapansi.
