ʻO ka protein beta-amyloid (1-42) kanaka, i ʻike ʻia ʻo Aβ 1-42, he kumu nui ia i ka wehe ʻana i nā mea huna o ka maʻi o Alzheimer.He mea koʻikoʻi kēia peptide i ka hoʻokumu ʻana i nā pā amyloid, nā pūʻulu enigmatic e hōʻino i ka lolo o nā maʻi o Alzheimer.Me ka hopena hoʻopōʻino, hoʻopau ia i ka kamaʻilio neuronal, hoʻoulu i ka mumū, a hoʻoulu i ka neurotoxicity, e alakaʻi ana i ka hōʻino cognitive a me ka pōʻino neural.ʻAʻole koʻikoʻi wale ka ʻimi ʻana i kāna ʻano hoʻohui a me nā mea ʻawaʻawa;He huakaʻi hoihoi ia i ka hoʻoponopono ʻana i ka puʻupuʻu Alzheimer a me ka hoʻomohala ʻana i nā lāʻau lapaʻau e hiki mai ana.
ʻO Aβ 1-42 kahi ʻāpana peptide o 42 amino acids i loaʻa mai ka ʻoki ʻana o ka amyloid precursor protein (APP) e nā β- a me γ-secretases.ʻO Aβ 1-42 kekahi o nā mea nui o ka amyloid plaques e hōʻiliʻili i loko o ka lolo o nā maʻi me ka maʻi o Alzheimer, kahi maʻi neurodegenerative i hōʻike ʻia e ka naʻau impairment a me ka nalowale hoʻomanaʻo.Ua hōʻike ʻia ʻo Aβ 1-42 i nā hana like ʻole a me nā noi i ka noiʻi olaola a me ka biomedical, e like me:
1.Neurotoxicity: Hiki i ka Aβ 1-42 ke hana i nā oligomers hiki ke hoʻopaʻa a hoʻopau i ka hana o nā neuronal membranes, receptors, and synapses.Hiki i kēia mau oligomers ke hoʻoulu i ke koʻikoʻi oxidative, mumū, a me ka apoptosis i nā neurons, e alakaʻi ana i ka nalowale synaptic a me ka make neuronal.Manaʻo ʻia ʻo Aβ 1-42 oligomers e ʻoi aku ka neurotoxic ma mua o nā ʻano ʻē aʻe o Aβ, e like me Aβ 1-40, ʻo ia ka ʻano nui loa o Aβ i loko o ka lolo.Manaʻo ʻia nā oligomers Aβ 1-42 e hiki ke hoʻolaha mai ka cell a cell, e like me nā prions, a hoʻoulu i ka misfolding a me ka hōʻuluʻulu ʻana o nā protein ʻē aʻe, e like me ka tau, ka mea e hana ai i nā neurofibrillary tangles i ka maʻi o Alzheimer.
Manaʻo nui ʻia ʻo Aβ 1-42 e like me ka isoform Aβ me ka neurotoxicity kiʻekiʻe loa.Ua hōʻike kekahi mau haʻawina hoʻokolohua i ka neurotoxicity o Aβ 1-42 me ka hoʻohana ʻana i nā ʻano like ʻole a me nā hiʻohiʻona.Eia kekahi laʻana, Lesné et al.(Brain, 2013) ua noiʻi i ka hoʻokumu ʻana a me nā mea ʻawaʻawa o Aβ oligomers, he mau mea hiki ke hoʻoheheʻe ʻia o Aβ monomers, a hōʻike ʻo Aβ 1-42 oligomers i ʻoi aku ka ikaika o ka hopena i nā neuronal synapses, e alakaʻi ana i ka emi ʻana o ka cognitive a me ka nalowale neuronal.Lambert et al.(Proceedings of the National Academy of Sciences, 1998) i hōʻike i ka neurotoxicity o Aβ 1-42 oligomers a ʻike ʻia he hopena koʻikoʻi ko lākou ma ka ʻōnaehana nerve waena, ma muli paha o ka hoʻopili ʻana i nā synapses a me nā neurotransmitters.ʻO Walsh et al.(Nature, 2002) i hōʻike i ka hopena inhibitory o Aβ 1-42 oligomers ma ka hippocampal long-term potentiation (LTP) i loko o vivo, ʻo ia kahi mīkini kelepona i lalo o ke aʻo ʻana a me ka hoʻomanaʻo.Hoʻopili ʻia kēia inhibition me ka hoʻomanaʻo a me ke aʻo ʻana, e hoʻoikaika ana i ka hopena o Aβ 1-42 oligomers ma ka synaptic plasticity.Shankar et al.(Nature Medicine, 2008) hoʻokaʻawale i nā dimer Aβ 1-42 pololei mai ka lolo o Alzheimer a hōʻike i ko lākou hopena i ka synaptic plasticity a me ka hoʻomanaʻo, e hāʻawi ana i nā hōʻike empirical no ka neurotoxicity o Aβ 1-42 oligomers.
Eia kekahi, ʻo Su et al.(Molecular & Cellular Toxicology, 2019) i hana i ka transcriptomics a me ka proteomics analysis of Aβ 1-42-induced neurotoxicity i SH-SY5Y neuroblastoma cell.Ua ʻike lākou i kekahi mau genes a me nā protein i hoʻopili ʻia e Aβ 1-42 i nā ala e pili ana i ke kaʻina apoptotic, ka unuhi ʻana i ka protein, ka cAMP catabolic process a me ka pane ʻana i ke koʻikoʻi endoplasmic reticulum.ʻO Takeda et al.(Biological Trace Element Research, 2020) i noiʻi i ka hana o ka extracellular Zn2+ i ka Aβ 1-42-induced neurotoxicity i ka maʻi o Alzheimer.Ua hōʻike lākou i ka Aβ 1-42-induced intracellular Zn2 + toxicity i hoʻonui ʻia me ka ʻelemakule ma muli o ka piʻi ʻana o ka makahiki i ka extracellular Zn2+.Ua manaʻo lākou e hūnā mau ʻia ʻo Aβ 1-42 mai nā terminal neuron e hoʻohaʻahaʻa i ka cognitive e pili ana i ka makahiki a me ka neurodegeneration ma o intracellular Zn2+ dysregulation.Ke hōʻike nei kēia mau haʻawina ʻo Aβ 1-42 kahi kumu nui i ka mediating neurotoxicity a me ka piʻi ʻana o ka maʻi i ka maʻi o Alzheimer ma o ka hoʻopili ʻana i nā kaʻina molecular a me nā kaʻina kelepona i loko o ka lolo.
2. Ka hana antimicrobial: Ua hōʻike ʻia ʻo Aβ 1-42 he hana antimicrobial e kūʻē i nā pathogens like ʻole, e like me ka bacteria, fungi, a me nā maʻi.Hiki i ka Aβ 1-42 ke hoʻopaʻa a hoʻopau i nā membrane o nā cell microbial, e alakaʻi ana i ko lākou lysis a me ka make.Hiki i ka Aβ 1-42 ke hoʻoikaika i ka ʻōnaehana immune innate a hoʻihoʻi i nā cell inflammatory i kahi o ka maʻi.Ua manaʻo kekahi mau haʻawina ʻo ka hōʻiliʻili ʻana o Aβ i loko o ka lolo he pane pale i nā maʻi maʻi a i ʻole nā hōʻeha.Eia nō naʻe, hiki i ka hana ʻana a i ʻole ka dysregulated o Aβ ke hoʻopōʻino i nā pūnaewele a me nā ʻiʻo.
Ua hōʻike ʻia ʻo Aβ 1-42 e hōʻike i ka hana antimicrobial e kūʻē i kahi ʻano o nā pathogens, e like me ka bacteria, fungi, a me nā maʻi, e like me Staphylococcus aureus, Escherichia coli, Candida albicans, a me Herpes simplex virus type 1, ma ka launa pū ʻana me ko lākou mau membrane a ke kumu o ko lakou haunaele a me ka lysis.ʻO Kumar et al.(Journal of Alzheimer's Disease, 2016) hōʻike i kēia hopena ma ka hōʻike ʻana ua hoʻololi ʻo Aβ 1-42 i ka membrane permeability a me ka morphology o nā cell microbial, e alakaʻi ana i ko lākou make.Ma waho aʻe o kāna hana antimicrobial pololei, hiki i ka Aβ 1-42 ke hoʻololi i ka pane kūlohelohe kūlohelohe a hoʻoulu i nā cell inflammatory i kahi o ka maʻi.Soscia et al.(PLoS One, 2010) i hōʻike i kēia kuleana ma ka hōʻike ʻana ua hoʻoulu ʻo Aβ 1-42 i ka hana ʻana o nā cytokines pro-inflammatory a me chemokines, e like me interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), a me ka macrophage inflammatory protein-1 alpha (MIP-1α), i nā microglia a me nā astrocytes, nā pūnaewele pale pale nui i ka lolo.
Kiʻi 2. Loaʻa i nā peptides Aβ ka hana antimicrobial.
(Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. ʻO ka amyloid beta-protein pili i ka maʻi Alzheimer he peptide antimicrobial. PLoS One 2010 Mar 3;5(3):e9505.)
ʻOiai ua manaʻo kekahi mau haʻawina ʻo ka hōʻiliʻili ʻana o Aβ i loko o ka lolo he pane pale ia i nā maʻi maʻi a i ʻole nā hōʻeha, no ka mea hiki iā Aβ ke hana ma ke ʻano he antimicrobial peptide (AMP) a hoʻopau i nā pathogens, ʻo ka paʻakikī paʻakikī ma waena o Aβ a me nā mea microbial e noho mau. kumuhana o ka hookolokolo ana.Hōʻike ʻia ke koena palupalu e ka noiʻi a Moir et al.(Journal of Alzheimer's Disease, 2018), e hōʻike ana i ka hana ʻole ʻana a i ʻole ka nui o ka hana Aβ hiki ke hoʻopōʻino i nā cell host a me nā ʻiʻo, e hōʻike ana i ke ʻano ʻelua o nā kuleana o Aβ i ka maʻi a me ka neurodegeneration.ʻO ka hana nui a dysregulated paha o Aβ hiki ke alakaʻi i kona hōʻuluʻulu a me ka waiho ʻana i loko o ka lolo, e hana ana i nā oligomers a me nā fibrils e hōʻino i ka hana neuronal a hoʻoulu i ka neuroinflammation.Hoʻopili ʻia kēia mau hana pathological me ka emi ʻana o ka naʻau a me ka nalowale hoʻomanaʻo i ka maʻi o Alzheimer, kahi maʻi neurodegenerative i hōʻike ʻia e ka dementia holomua.No laila, he mea koʻikoʻi ke kaulike ma waena o nā hopena maikaʻi a maikaʻi ʻole o Aβ no ka mālama ʻana i ke olakino lolo a pale i ka neurodegeneration.
3.Iron export: Ua hōʻike ʻia ʻo Aβ 1-42 i ka hoʻoponopono ʻana i ka homeostasis hao ma ka lolo.He mea koʻikoʻi ka hao no nā kaʻina olaola he nui, akā hiki i ka hao ke hoʻoulu i ke kaumaha oxidative a me ka neurodegeneration.Hiki i ka Aβ 1-42 ke hoʻopaʻa i ka hao a hoʻomaʻamaʻa i kāna lawe ʻana mai nā neurons ma o ferroportin, kahi mea lawe hao transmembrane.Hiki i kēia ke kōkua i ka pale ʻana i ka hōʻiliʻili hao a me nā mea ʻawaʻawa i loko o ka lolo, no ka mea, hiki i ka hao ke hoʻoulu i ke kaumaha oxidative a me ka neurodegeneration.ʻO Duce et al.(Cell, 2010) i hōʻike i ka Aβ 1-42 i hoʻopaʻa ʻia i ka ferroportin a hoʻonui i kāna hōʻike a me kāna hana i nā neurons, e alakaʻi ana i ka emi ʻana o nā pae hao intracellular.Ua hōʻike pū lākou ua hōʻemi ʻo Aβ 1-42 i ka hōʻike ʻana o ka hepcidin, kahi hormone e kāohi ai i ka ferroportin, i nā astrocytes, e hoʻonui hou i ka hao mai nā neurons.Eia naʻe, ʻoi aku ka maʻalahi o ka Aβ i hoʻopaʻa ʻia i ka hao i ka hōʻuluʻulu ʻana a me ka waiho ʻana i loko o ke kikowaena extracellular, e hana ana i nā pā amyloid.ʻO Ayton et al.(Journal of Biological Chemistry, 2015) i hōʻike i ka hao i hāpai i ka hoʻokumu ʻana o Aβ oligomers a me nā fibrils in vitro a in vivo.Ua hōʻike pū lākou i ka hao chelation i hōʻemi i ka Aβ aggregation a me ka waiho ʻana i nā ʻiole transgenic.No laila, he mea koʻikoʻi ke kaulike ma waena o nā hopena maikaʻi a maikaʻi ʻole o Aβ 1-42 ma ka homeostasis hao no ka mālama ʻana i ke olakino lolo a pale i ka neurodegeneration.
He mea hana polypeptide mākou ma Kina, me nā makahiki he nui o ka ʻike makua i ka hana polypeptide.ʻO Hangzhou Taijia Biotech Co., Ltd. he mea hana ʻoihana polypeptide raw material, hiki ke hāʻawi i nā ʻumi kaukani o ka polypeptide raw material a hiki ke hana ʻia e like me nā pono.He maikaʻi ka maikaʻi o nā huahana polypeptide, a hiki i ka maʻemaʻe ke hiki i ka 98%, iʻikeʻia e nā mea hoʻohana ma ka honua holoʻokoʻa.Welcome e nīnau iā mākou.
