Alterations in Neuronal Nicotinic Acetylcholine Receptors in the Pathogenesis of Various Cognitive Impairments

CNS Neurosci Ther. 2024 Oct;30(10):e70069. doi: 10.1111/cns.70069.

Abstract

Cognitive impairment is a typical symptom of both neurodegenerative and certain other diseases. In connection with these different pathologies, the etiology and neurological and metabolic changes associated with cognitive impairment must differ. Until these characteristics and differences are understood in greater detail, pharmacological treatment of the different forms of cognitive impairment remains suboptimal. Neurotransmitter receptors, including neuronal nicotinic acetylcholine receptors (nAChRs), dopamine receptors, and glutamine receptors, play key roles in the functions and metabolisms of the brain. Among these, the role of nAChRs in the development of cognitive impairment has attracted more and more attention. The present review summarizes what is presently known concerning the structure, distribution, metabolism, and function of nAChRs, as well as their involvement in major cognitive disorders such as Alzheimer's disease, Parkinson's disease, vascular dementia, schizophrenia, and diabetes mellitus. As will be discussed, the relevant scientific literature reveals clearly that the α4β2 and α7 nAChR subtypes and/or subunits of the receptors play major roles in maintaining cognitive function and in neuroprotection of the brain. Accordingly, focusing on these as targets of drug therapy can be expected to lead to breakthroughs in the treatment of cognitive disorders such as AD and schizophrenia.

Keywords: Alzheimer's disease; Parkinson's disease; cognitive disorder; diabetes mellitus; nicotinic acetylcholine receptors; schizophrenia; vascular dementia.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Cognition Disorders / metabolism
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Humans
  • Neurons / metabolism
  • Receptors, Nicotinic* / metabolism

Substances

  • Receptors, Nicotinic