Abstract
Amyloid plaques, derived from aggregates of amyloid β (Aβ), are closely linked to the pathogenesis of Alzheimer’s disease (AD). Another neuropathological hallmark is the loss of cholinergic markers, associated with a reduction in the α7 subunit of the nicotinic acetylcholine receptor (nAChR) in the brains of AD patients. The α7-nAChR plays an important role in circuits involved in learning and memory, and may be a promising target for the treatment of AD. Numerous studies indicate that binding to α7-nAChRs is neuroprotective. However, Aβ has also been shown to induce tau phosphorylation via α7-nAChR activation. In addition, picomolar to nanomolar concentrations of Aβ stimulate presynaptic α7-nAChRs, evoking an increase in presynaptic Ca2+ levels. There is evidence that Aβ influences hippocampus-dependent cognitive functions and synaptic plasticity such as long-term potentiation by modulating the function of α7-nAChRs. In line with the roles of α7-nAChRs in AD pathogenesis, allosteric modulators of α7-nAChRs have been proposed as novel therapeutical agents in the treatment of this disease.
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Abbreviations
- ACh:
-
Acetylcholine
- AChE:
-
Acetylcholinesterase
- AD:
-
Alzheimer’s disease
- APP:
-
Aβ precursor protein
- APPswe:
-
Swedish APP 670/671 mutation
- Aβ:
-
Amyloid-β
- ChAT:
-
Choline acetyltransferase
- ERK/MAPK:
-
Extracellular-signal-regulated kinase mitogen-activated protein kinase
- GSK3beta:
-
Glycogen synthase kinase3β
- HEPES:
-
4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid
- LDH:
-
Lactate dehydrogenase
- LTD:
-
Long term depression
- LTP:
-
Long term potentiation
- MCI:
-
Mild cognitive impairment
- MLA:
-
Methyllycaconitine
- nAChR:
-
Nicotinic acetylcholine receptor
- NMDA:
-
N-methyl-d-aspartate
- siRNA:
-
Small interfering RNA
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The authors gratefully acknowledge Derek Boyd for his skillful assistance in preparing the manuscript.
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Oz, M., Petroianu, G., Lorke, D.E. (2016). α7-Nicotinic Acetylcholine Receptors: New Therapeutic Avenues in Alzheimer’s Disease. In: Li, M. (eds) Nicotinic Acetylcholine Receptor Technologies. Neuromethods, vol 117. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3768-4_9
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