| Autor: |
Khan, Ghous M., Tong, Mei, Jhun, Michelle, Arora, Komal, Nichols, Robert A. |
| Předmět: |
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| Zdroj: |
European Journal of Neuroscience; Mar2010, Vol. 31 Issue 5, p788-796, 9p, 1 Diagram, 4 Graphs |
| Abstrakt: |
Beta amyloid (Aβ) plays a central role in the pathogenesis of Alzheimer’s disease. Aβ is the major constituent of senile plaques, but there is a significant presence of Aβ in the brain in soluble forms. The results of functional studies indicate that soluble Aβ interacts with the α7 nicotinic acetylcholine receptor (nAChR) complex with apparent high affinity. However, conflicting data exist as to the nature of the Aβ–α7 nAChR interaction, and whether it is the result of specific binding. Moreover, both agonist-like and antagonist-like effects have been reported. In particular, agonist-like effects have been observed for presynaptic nAChRs. Here, we demonstrate Aβ1-42-evoked stimulatory changes in presynaptic Ca2+ level via exogenous α7 nAChRs expressed in the axonal varicosities of differentiated hybrid neuroblastoma NG108-15 cells as a model, presynaptic system. The Aβ1-42-evoked responses were concentration-dependent and were sensitive to the highly selective α7 nAChR antagonist α-bungarotoxin. Voltage-gated Ca2+ channels and internal Ca2+ stores were both involved in Aβ1-42-evoked increases in presynaptic Ca2+ following activation of α7 nAChRs. In addition, disruption of lipid rafts by cholesterol depletion led to substantially attenuated responses to Aβ1-42, whereas responses to nicotine were largely intact. These results directly implicate the nicotinic receptor complex as a target for the agonist-like action of pico- to nanomolar concentrations of soluble Aβ1-42 on the presynaptic nerve terminal, including the possible involvement of receptor-associated lipid rafts. This interaction probably plays an important neuromodulatory role in synaptic dynamics. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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