Protection against the Neurotoxic Effects of β-Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of α7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases.

Protection against the Neurotoxic Effects of β-Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of α7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases. Am J Pathol. 2018 Jan 13;: Authors: Zhao L, Xiao Y, Xiu J, Tan LC, Guan ZZ Abstract The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP) , expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase in primary cultured neurons and SH-SY5Y cells over-expressing human APP670/671. Lovastatin attenuated the neurotoxic effects of β-amyloid peptide (Aβ) and affected the metabolism of APP, reducing levels of Aβ1-42 and BACE1; enhancing those of αAPP, ADAM10, and BACE2; and up-regulating expression of α7 nAChR and stimulating phosphoylation of ERK1/2. Interestingly, methyllycaconitine, an antagonist of α7 nAChR, attenuated this effect on αAPP, but not on phospho-ERK1/2; whereas U0126, an inhibitor of MEK/ERK, blocked both the elevated expression of α7 nAChR and enhanced secretion of αAPP. Our findings indicate that lovastatin up-regulates expression of α7 nAChR via...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research