Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicity.
Int J Biochem Cell Biol
; 45(4): 899-907, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23353645
ABSTRACT
Aggregated amyloid-ß 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-ß are mediated through the interaction of the peptide with α7-type nicotinic acetylcholine receptors at the cell surface. Here we demonstrated that affinity purified antibodies to synthetic fragment 173-193 of the α7-subunit of the nAChR are able to protect cells from amyloid-ß induced cell death. The antibodies had no effect on the amyloid-ß induced calcium signal in astrocytes. However, they significantly reduced amyloid-ß 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 α7-type nicotinic acetylcholine receptors α-bungarotoxin was vital in inhibiting both amyloid-ß induced ROS production, caspase 3 cleavage as well as cell death. The uncovered details of the mechanism underlying the action of antibodies to α7-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Acetilcolina
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Astrócitos
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Peptídeos beta-Amiloides
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Receptores Nicotínicos
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Anticorpos
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Neurônios
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article