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α7-Nicotinic Acetylcholine Receptors: New Therapeutic Avenues in Alzheimer’s Disease

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Nicotinic Acetylcholine Receptor Technologies

Part of the book series: Neuromethods ((NM,volume 117))

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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Acknowledgement

The authors gratefully acknowledge Derek Boyd for his skillful assistance in preparing the manuscript.

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Authors and Affiliations

  1. Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA

    Murat Oz M.D., Ph.D. & Georg Petroianu

  2. Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates

    Murat Oz M.D., Ph.D. & Dietrich E. Lorke

Authors
  1. Murat Oz M.D., Ph.D.
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  2. Georg Petroianu
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  3. Dietrich E. Lorke
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Correspondence to Murat Oz M.D., Ph.D. .

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  1. University of Virginia, Charlottesville, Virginia, USA

    Ming D. Li

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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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  • DOI: https://doi.org/10.1007/978-1-4939-3768-4_9

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