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

FEBS Lett. 2022 Nov;596(22):2914-2927. doi: 10.1002/1873-3468.14467. Epub 2022 Aug 15.

Abstract

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 AβΟ-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 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.

Keywords: 67 kDa laminin receptor; PACAP; amyloid-β; cAMP; cellular prion protein; protein kinase A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides* / metabolism
  • Cell Death
  • Laminin / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • PrPC Proteins* / metabolism
  • Prion Proteins
  • Receptors, Laminin / genetics

Substances

  • Amyloid beta-Peptides
  • Prion Proteins
  • PrPC Proteins
  • Laminin
  • Receptors, Laminin
  • Pituitary Adenylate Cyclase-Activating Polypeptide