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

Abstract

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

Resveratrol and its metabolites elicit neuroprotection via high‐affinity binding to the laminin receptor at low nanomolar concentrations

“…Previously we found 67LR distributed on the cell surface of NS-1 cells [36,50]. The current study found that t-RES-3-G activates the cAMP/PKA/Epac signaling pathways.…”