Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment

Neuropharmacology. 2015 Sep;96(Pt B):255-62. doi: 10.1016/j.neuropharm.2014.11.018. Epub 2014 Dec 13.

Abstract

Alzheimer's Disease (AD) is the major form of senile dementia, characterized by neuronal loss, extracellular deposits, and neurofibrillary tangles. It is accompanied by a loss of cholinergic tone, and acetylcholine (ACh) levels in the brain, which were hypothesized to be responsible for the cognitive decline observed in AD. Current medication is restricted to enhancing cholinergic signalling for symptomatic treatment of AD patients. The nicotinic acetylcholine receptor family (nAChR) and the muscarinic acetylcholine receptor family (mAChR) are the target of ACh in the brain. Both families of receptors are affected in AD. It was demonstrated that amyloid beta (Aβ) interacts with nAChRs. Here we discuss how Aβ activates or inhibits nAChRs, and how this interaction contributes to AD pathology. We will discuss the potential role of nAChRs as therapeutic targets. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.

Keywords: Alzheimer's disease; Aβ peptide; Cholinergic system; Nicotine; Nicotinic receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice, Transgenic
  • Neurons / metabolism
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Receptors, Muscarinic / metabolism*
  • Receptors, Nicotinic / metabolism*

Substances

  • Amyloid beta-Peptides
  • Nicotinic Agonists
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • Nicotine