Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicity.

ABSTRACT: Aggregated amyloid-? causes pathological changes in mixed cultures of neurons and astrocytes such as sporadic cytoplasmic intracellular Ca(2+)-signalling, increase in reactive oxygen species production and cell death. Some of the toxic effects of amyloid-? are mediated through the interaction of the peptide with ?7-type nicotinic acetylcholine receptors at the cell surface. Here we demonstrated that affinity purified antibodies to synthetic fragment 173-193 of the ?7-subunit of the nAChR are able to protect cells from amyloid-? induced cell death. The antibodies had no effect on the amyloid-? induced calcium signal in astrocytes. However, they significantly reduced amyloid-? induced and NADPH oxidase mediated ROS production. Modulation of the NADPH oxidase activity by either the antibodies, the receptor agonist acetylcholine or the antagonist of the ?7-type nicotinic acetylcholine receptors ?-bungarotoxin was vital in inhibiting both amyloid-? induced ROS production, caspase 3 cleavage as well as cell death. The uncovered details of the mechanism underlying the action of antibodies to ?7-type nicotinic acetylcholine receptors gives additional insight into the involvement of this receptor in Alzheimer's disease pathology and provides a new approach to anti-Alzheimer's disease vaccine design.

SUBMITTER: Kamynina AV 

PROVIDER: S-EPMC4208291 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature