@Article{Adamczyk2005,
journal="Folia Neuropathologica",
issn="1641-4640",
volume="43",
number="3",
year="2005",
title="Original articleAlzheimer\'s disease related peptides affected cholinergic receptor mediated poly(ADP-ribose) polymerase activity in the hippocampus",
abstract="Our previous studies indicated that Alzheimer\'s disease (AD) related amyloid beta peptide (A\β) significantly altered muscarinic cholinergic receptor (mChR) signaling on the level of G protein regulated phospholipase C (PLC) leading to the lower formation of inositol-1,4,5-triphosphate (IP 3 ) and diacylglycerol (DAG). Recent studies indicated that poly (ADP-ribose) polymerase-1 (PARP-1) is a new nuclear target in signal transduction pathway in the brain. In this study the effect of A\β 25-35 (25 \µM) and non-A\β component of Alzheimer\'s disease amyloid (NAC, 10 \µM) on mChR-dependent signaling to PARP-1 was determined. PARP-1 activity was estimated radiochemically using egzogenous substrate adenine[14C]NAD. The results showed that the non hydrolysable agonist of mChR, carbachol (1 mM) together with GTP(g)S (100 \µM) stimulated PARP-1 activity in the hippocampus by about 100%. TMB-8, inhibitor of IP 3  receptor decreased PARP-1 activation evoked by carbachol/GTP(g)S. Stimulation of mChR did not lead to free radicals generation but activate PARP-1 through IP 3 /Ca2+ regulated processes. This cholinergic receptor dependent PARP-1 activation was abolished by A\β and NAC peptide. These toxic peptides themselves significantly stimulated PARP-1 activity by free radicals mediated DNA damage. These data indicated that A\β and NAC peptide affected mChR-dependent signal transduction to PARP-1 probably through free radicals evoked inhibition of IP 3  formation by phospholipase C.",
author="Adamczyk, Agata
and Jęśko, Henryk
and Strosznajder, Robert Piotr",
pages="139--142",
url="https://www.termedia.pl/Original-article-Alzheimer-s-disease-related-peptides-affected-cholinergic-receptor-mediated-poly-ADP-ribose-polymerase-activity-in-the-hippocampus,20,3760,1,1.html"
}