Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (12): 2675-2676.doi: 10.4103/1673-5374.373664

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Cyclic adenosine monophosphate-elevating agents inhibit amyloid-beta internalization and neurotoxicity: their action in Alzheimer’s disease prevention

Rayudu Gopalakrishna*, Andrew Oh, Narayan R. Bhat, William J. Mack   

  1. Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA (Gopalakrishna R, Oh A)
    Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA (Mack WJ)
    Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA (Bhat NR)
  • Online:2023-12-15 Published:2023-06-14
  • Contact: Rayudu Gopalakrishna, PhD, rgopalak@usc.edu.
  • Supported by:
    This work was supported by NIH grants, NINDS R21 NS116720 and NINDS/NIA RF1 NS130681 (to RG and WJM) and NIA R21 AG059422 (to NRB). 

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Abstract: Recently, we have found that various intracellular cyclic adenosine monophosphate (cAMP)-elevating agents, both pharmacological (dibutyryl-cAMP, forskolin, and rolipram) and physiological (pituitary adenylate cyclase-activating polypeptide), decrease cell-surface levels of 67-kDa laminin receptor (67LR) and cellular prion protein (PrPC). Thereby, they inhibit the internalization of amyloid-β oligomer (AβO) and attenuate AβO-induced neuronal death (Figure 1; Gopalakrishna et al., 2022). We postulate that the 67LR-PrPC-mediated AβO mechanism may be important in understanding the Alzheimer’s disease (AD)-preventive actions of green tea polyphenol, epigallocatechin-3-gallate (EGCG), which is known to bind 67LR at a site within the PrPC-binding site and induce 67LR internalization. This mechanism may also be relevant in understanding the anti-AD actions of dietary agents such as resveratrol and quercetin as well as synthetic drugs (including the ones in clinical trials) that elevate intracellular cAMP by inhibiting cyclic nucleotide phosphodiesterases (PDEs).