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

被引：4

作者：

Gopalakrishna, Rayudu ^{[1
]}

Lin, Charlotte Y. ^{[1
]}

Oh, Andrew ^{[1
]}

Le, Calvin ^{[1
]}

Yang, Seolyn ^{[1
]}

Hicks, Alexandra ^{[1
]}

Kindy, Mark S. ^{[2
,3
]}

Mack, William J. ^{[4
]}

Bhat, Narayan R. ^{[5
]}

机构：

[1] Univ Southern Calif, Keck Sch Med, Dept Integrat Anat Sci, 1333 San Pablo St, Los Angeles, CA 90089 USA

[2] Univ S Florida, Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33620 USA

[3] James A Haley VA Med Ctr, Tampa, FL USA

[4] Univ Southern Calif, Keck Sch Med, Dept Neurol Surg, Los Angeles, CA 90007 USA

[5] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA

来源：

FEBS LETTERS | 2022年 / 596卷 / 22期

基金：

美国国家卫生研究院;

关键词：

67 kDa laminin receptor; amyloid-beta; cAMP; cellular prion protein; PACAP; protein kinase A; CYCLASE-ACTIVATING POLYPEPTIDE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; ANTIOXIDANT CAPACITY; CULTURE; EXPRESSION; PEPTIDE; PACAP; ENDOCYTOSIS; HYPOTHESIS;

D O I：

10.1002/1873-3468.14467

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous studies have shown that amyloid-beta oligomers (A beta O) bind with high affinity to cellular prion protein (PrPC). The A beta O-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 A beta O and A beta Omicron-induced cell death. Both pharmacological (dibutyryl-cAMP, forskolin and rolipram) and physiological (pituitary adenylate cyclase-activating polypeptide) cAMP-elevating agents decreased cell-surface PrPC and 67LR, thereby attenuating the uptake of A beta O 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 A beta O-induced cytotoxicity by decreasing cell-surface-associated PrPC and 67LR.

引用

页码：2914 / 2927

页数：14

共 49 条

[1] PHENOL RED IN TISSUE-CULTURE MEDIA IS A WEAK ESTROGEN - IMPLICATIONS CONCERNING THE STUDY OF ESTROGEN-RESPONSIVE CELLS IN CULTURE [J].