title: Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide.
abstract: Alzheimer's disease (AD) pathology is characterized by plaques, tangles, and neuronal cell loss. The main constituent of plaques is beta-amyloid peptide (A beta), a 39-42 residue peptide which has been linked to disruption of calcium homeostasis and neurotoxicity in vitro. We demonstrate that a neurotoxic fragment of A beta, A beta (25-35) spontaneously inserted into planar lipid membranes to form weakly selective, voltage dependent, ion-permeable channels. We suggest that channel formation may be involved in the pathogenesis of AD and that A beta (25-35) may be the active channel forming segment.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute.
authors.forename: T
authors.initials: T
authors.lastname: Mirzabekov
authors.forename: M C
authors.initials: MC
authors.lastname: Lin
authors.forename: W L
authors.initials: WL
authors.lastname: Yuan
authors.forename: P J
authors.initials: PJ
authors.lastname: Marshall
authors.forename: M
authors.initials: M
authors.lastname: Carman
authors.forename: K
authors.initials: K
authors.lastname: Tomaselli
authors.forename: I
authors.initials: I
authors.lastname: Lieberburg
authors.forename: B L
authors.initials: BL
authors.lastname: Kagan
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002712:Chlorides; D007473:Ion Channels; D008051:Lipid Bilayers; D010446:Peptide Fragments; D012964:Sodium; D011188:Potassium; D002118:Calcium