title: Cholinergic Mechanisms in the Cerebral Cortex: Beyond Synaptic Transmission.
abstract: Functional overviews of cholinergic mechanisms in the cerebral cortex have traditionally focused on the release of acetylcholine with modulator and transmitter effects. Recently, however, data have emerged that extend the role of acetylcholine and cholinergic innervations to a range of housekeeping and metabolic functions. These include regulation of amyloid precursor protein (APP) processing with production of amyloid β (Aβ) and other APP fragments and control of the phosphorylation of microtubule-associated protein (MAP) tau. Evidence has been also presented for receptor-ligand like interactions of cholinergic receptors with soluble Aβ peptide and MAP tau, with modulator and signaling effects. Moreover, high-affinity binding of Aβ to the neurotrophin receptor p75 (p75NTR) enriched in basalo-cortical cholinergic projections has been implicated in clearance of Aβ and nucleation of amyloid plaques. Here, we critically evaluate these unorthodox cholinergic mechanisms and discuss their role in neuronal physiology and the biology of Alzheimer's disease.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Faculty of Science and Health, School of Biotechnology, Dublin City University, Dublin, Ireland saak.ovsepian@gmail.com.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Zaborszky
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000378:metabolism; D006801:Humans; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D009435:Synaptic Transmission; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011950:Receptors, Cholinergic; D016875:tau Proteins; D000109:Acetylcholine
keywords: Alzheimer’s disease; acetylcholine; amyloid β; p75 neurotrophin receptor; tau protein; volume transmission