title: Positive modulators of the α7 nicotinic receptor against neuroinflammation and cognitive impairment in Alzheimer's disease.
abstract: Evidence so far indicates that therapies targeting a single aspect of Alzheimer's disease (AD) have no sufficient efficacy in diminishing long-term the progression of AD. Neuroinflammation is an early event during the development of the disease and it is thought to exacerbate the abnormal aggregation of the amyloid beta peptide (Aβ) and the microtubule associated protein Tau. Inhibition of gliosis is considered fundamental to reduce neuroinflammation, oxidative stress, apoptosis and synaptic dysfunction driving the progression of AD. Drugs that are able to target more than one aspect of the pathology may have higher chances of success. Modulators of α7 nicotinic acetylcholine receptors (α7nAChRs) such as nicotine and some of its derivatives have this potential because of their anti-inflammatory, anti-apoptotic, pro-cognitive and anti-protein aggregation effects. However, the rapid desensitization of α7nAChRs is considered an important factor limiting its potential therapeutic use. In here, in light of current evidence, the objective of this review is to discuss the advantages and potential therapeutic value of positive allosteric modulators (PAMs) of the nAChRs in halting or delaying the progression of AD by diminishing neuroinflammation, abnormal protein aggregation and synaptic dysfunction.
authors.affiliation: Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur, 1457 Concepción, Chile; Research & Development Service, Bay Pines VA Healthcare System, Bay Pines, FL 33744, USA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33647, USA. Electronic address: echeverria.valentina@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
authors.affiliation: Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur, 1457 Concepción, Chile.
authors.forename: Alex
authors.initials: A
authors.lastname: Yarkov
authors.affiliation: GALLY International Biomedical Research Consulting LLC, San Antonio, TX, USA; School of Health Science and Healthcare Administration, University of Atlanta, Johns Creek, GA 30097, USA.
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Alzheimer's disease; Autoimmunity; Glia; Neuroinflammation; Nicotinic receptors; Prostaglandins