cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-β uptake and amyloid-β-induced neuronal cell death.

cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-β uptake and amyloid-β-induced neuronal cell death.
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cAMP 诱导的细胞表面层粘连蛋白受体和细胞朊病毒蛋白的减少减弱了淀粉样蛋白 β 的摄取和淀粉样蛋白 β 诱导的神经元细胞死亡。

DOI:
10.1002/1873-3468.14467
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发表时间:
2022-11
期刊:
影响因子:
3.5
通讯作者:
Bhat, Narayan R.
Bhat, Narayan R.
中科院分区:
生物学3区
文献类型:
--
作者:
Gopalakrishna, Rayudu;Lin, Charlotte Y.;Oh, Andrew;Le, Calvin;Yang, Seolyn;Hicks, Alexandra;Kindy, Mark S.;Mack, William J.;Bhat, Narayan R.

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先前的研究表明,淀粉样β寡聚体(AβO)与细胞朊蛋白(PrPC)具有高亲和力结合。AβO-PrPC复合物与细胞表面共受体结合,包括层粘连蛋白受体(67 LR)。我们目前的研究表明,在Neuroscreen-1细胞中,67 LR是参与细胞摄取AβO和Aβ O诱导细胞死亡的主要共受体。药理学(二丁酰-cAMP、毛喉素、咯利普兰)和生理学(垂体腺苷酸环化酶激活多肽)cAMP升高剂均降低细胞表面PrPC和67 LR,从而减弱AβO的摄取和导致的神经元细胞死亡。这些cAMP保护作用依赖于蛋白激酶A,但不依赖于cAMP直接激活的交换蛋白。cAMP可能通过减少细胞表面结合的PrPC和67 LR来保护神经细胞免受Aβ O诱导的细胞毒性。
Previous studies have shown that amyloid-β oligomers (AβO) bind with high affinity to cellular prion protein (PrPC). The AβO-PrPC complex binds to cell-surface co-receptors, including the laminin receptor (67LR). Our current studies revealed that in Neuroscreen-1 cells, 67LR is the major co-receptor involved in the cellular uptake of AβO and AβO-induced cell death. Both pharmacological (dibutyryl-cAMP, forskolin, rolipram) and physiological (pituitary adenylate cyclase-activating polypeptide) cAMP-elevating agents decreased cell-surface PrPC and 67LR, thereby attenuating the uptake of AβO and the resultant neuronal cell death. These cAMP protective effects are dependent on protein kinase A, but not dependent on the exchange protein directly activated by cAMP. Conceivably, cAMP protects neuronal cells from AβO-induced cytotoxicity by decreasing cell-surface associated PrPC and 67LR.
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