title: Neurotoxicity of amyloid β-protein: synaptic and network dysfunction.
abstract: Evidence for an ever-expanding variety of molecular mediators of amyloid β-protein neurotoxicity (membrane lipids, receptor proteins, channel proteins, second messengers and related signaling cascades, cytoskeletal proteins, inflammatory mediators, etc.) has led to the notion that the binding of hydrophobic Aβ assemblies to cellular membranes triggers multiple effects affecting diverse pathways. It appears unlikely that there are only one or two cognate receptors for neurotoxic forms of Aβ and also that there are just one or two assembly forms of the peptide that induce neuronal dysfunction. Rather, various soluble (diffusible) oligomers of Aβ that may be in dynamic equilibrium with insoluble, fibrillar deposits (amyloid plaques) and that can bind to different components of neuronal and non-neuronal plasma membranes appear to induce complex patterns of synaptic dysfunction and network disorganization that underlie the intermittent but gradually progressive cognitive manifestations of the clinical disorder. Modern analyses of this problem utilize electrophysiology coupled with synaptic biochemistry and behavioral phenotyping of animal models to elucidate the affected circuits and assess the effects of potential therapeutic interventions.
authors: Gladstone Institute of Neurological Disease and University of California, San Francisco, San Francisco, California, USA. lmucke@gladstone.ucsf.edu
authors: Lennart
authors: L
authors: Mucke
authors: Dennis J
authors: DJ
authors: Selkoe
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D009415:Nerve Net / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D016229:Amyloid beta-Peptides