The international journal of biochemistry & cell biology, 2013-04, Vol.45 (4), p.899-907
2013
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- Autor(en) / Beteiligte
- Titel
- Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicity
- Ist Teil von
- The international journal of biochemistry & cell biology, 2013-04, Vol.45 (4), p.899-907
- Ort / Verlag
- Netherlands: Elsevier Ltd
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- ► Antibodies to α7 acetylcholine receptors protect against Aβ-induced cell death. ► Acetylcholine and AchRabs significantly reduce Aβ-induced ROS production. ► Acetylcholine pathway modulates the activity of the NADPH oxidase. ► Acetylcholine and AchRabs do not affect the Aβ-induced Ca2+-signal. Aggregated amyloid-β 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-β 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-β induced cell death. The antibodies had no effect on the amyloid-β induced calcium signal in astrocytes. However, they significantly reduced amyloid-β 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-β 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1357-2725eISSN: 1878-5875DOI: 10.1016/j.biocel.2013.01.011Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4208291
- Format
- –
- Schlagworte
- acetylcholine, Acetylcholine - pharmacology, agonists, alpha7 Nicotinic Acetylcholine Receptor, Alzheimer disease, Amyloid beta-Peptides - toxicity, Animals, antagonists, antibodies, Antibodies - immunology, astrocytes, Astrocytes - cytology, Astrocytes - drug effects, Astrocytes - metabolism, Ca2, calcium signaling, Calcium Signaling - drug effects, Caspase 3 - metabolism, caspase-3, cell death, Cell Death - drug effects, cholinergic receptors, Enzyme Activation - drug effects, mixed culture, NAD(P)H oxidase (H2O2-forming), NADPH oxidase, neurons, Neurons - cytology, Neurons - drug effects, Neurons - metabolism, Peptide Fragments - toxicity, Rats, Rats, Sprague-Dawley, Reactive oxygen species, Reactive Oxygen Species - metabolism, Receptors, Nicotinic - immunology, toxicity, vaccine development, α7-Type nicotinic acetylcholine receptors, β-Amyloid