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

作者：Kamynina Anna V; Holmstroem Kira M; Koroev Dmitriy O; Volpina Olga M; Abramov Andrey Y^*

来源：International Journal of Biochemistry & Cell Biology, 2013, 45(4): 899-907.

DOI：10.1016/j.biocel.2013.01.011

• beta-Amyloid
• NADPH oxidase
• Ca2+
• alpha 7-Type nicotinic acetylcholine receptors
• Reactive oxygen species

Aggregated amyloid-beta causes pathological changes in mixed cultures of neurons and astrocytes such as sporadic cytoplasmic intracellular Ca2+-signalling, increase in reactive oxygen species production and cell death. Some of the toxic effects of amyloid-beta are mediated through the interaction of the peptide with alpha 7-type nicotinic acetylcholine receptors at the cell surface. Here we demonstrated that affinity purified antibodies to synthetic fragment 173-193 of the alpha 7-subunit of the nAChR are able to protect cells from amyloid-beta induced cell death. The antibodies had no effect on the amyloid-beta induced calcium signal in astrocytes. However, they significantly reduced amyloid-beta 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 alpha 7-type nicotinic acetylcholine receptors alpha-bungarotoxin was vital in inhibiting both amyloid-beta induced ROS production, caspase 3 cleavage as well as cell death. The uncovered details of the mechanism underlying the action of antibodies to alpha 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.

• 出版日期2013-4