阿尔茨海默病(AD)是全世界最常见的痴呆症,代表了现代医学中最具挑战性的领域。越来越多的证据表明,中枢神经系统中Aβ的积累在AD发病机制中起着关键作用。因此,靶向Aβ及其聚集形式已被用于治疗和疾病诊断。然而,血脑屏障(BBB)的限制严重阻碍了神经治疗药物的输送。因此,开发兼具BBB渗透性和高Aβ靶向性的纳米载体有望在AD治疗中发挥重要作用。研究表明,载脂蛋白APOE可以与Aβ结合,并以脂质状态和APOE亚型依赖的方式促进Aβ清除。同时,APOE还可以共定位新形成的Aβ沉积物。这些信息表明,APOE可能是Aβ靶向药物的天然纳米载体。
“透视说”:APOE功能
APOE的结构区域和功能区域示意图
“主流说”:APOE与Aβ
大脑中APOE与Aβ的代谢示意图
“策略说”:APOE与AD
靶向APOE治疗AD的策略
“靶心说”:APOE与其他神经退行性疾病
APOE及其相关疾病
小编有话说
前述研究强调了APOE在神经退行性疾病中促进作用,包括APOE显著影响中枢神经系统细胞功能,并影响AD和其他以明显炎症为特征的中枢神经系统疾病的进展。然而,APOE的生理学及其在神经退行性疾病中的意义仍有很多需要研究和学习的地方。针对APOE的临床研究,将对弄清APOE在神经炎症和神经变性中的作用具有重要价值。APOE的靶向性及与致病性的相互联系将为AD及其他相关的疾病预防和治疗提供巨大的潜力空间。
ACROBiosystems百普赛斯开发了APOE系列蛋白,高纯度经SDS-PAGE及SEC-MALS验证,结合TREM2和LDLR的高生物活性经BLI、SPR验证,递送LNPs-siRNA的能力经FACS验证,助力AD及其他相关疾病治疗药物研发。
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验证数据
Loaded Biotinylated Human TREM2, His,Avitag (Cat. No. TR2-H82E7) on SA Biosensor, can bind Human APOE2 (R154S), His Tag (Cat. No. APE-H5256) with an affinity constant of 2.08 nM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).
Human LDL R, Fc Tag (Cat. No. LDR-H5254) captured on CM5 chip via Anti-human IgG Fc antibodies surface can bind Human APOE2, His Tag (Cat. No. APE-H52H6) with an affinity constant of 16.2 nM as determined in a SPR assay (Biacore 8K) (QC tested).
★ APOE递送LNPs-siRNA的能力经FACS验证
3e5 of HeLa cells were co-incubated with 50 nM Cy3-labeled LNPs-siRNA in the presence or absence of 1 μg/mL Human APOE3, His Tag (Cat. No. APE-H5246), washed and analyzed with FACS. PE signal was used to evaluate the expression of Cy3+ HeLa cells (Routinely tested).
点击了解更多AD药物研发相关蛋白
APOE | APP/A beta | ACHE | BACE1 | BCHE |
GSK-3beta | Tau | TREM2 | NPTX2 | GRIN2B |
推荐阅读:细说:APOE和阿尔茨海默病
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参考文献
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5. Kok E, Haikonen S, Luoto T, et al. Apolipoprotein E–dependent accumulation of Alzheimer disease–related lesions begins in middle age[J]. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 2009, 65(6): 650-657. https://doi.org/10.1002/ana.21696.