Membrane currents induced in Xenopus oocytes by the C-terminal fragment of the beta-amyloid precursor protein.
There is mounting evidence that at least some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the beta-amyloid precursor protein (beta APP). Most research has focused on the amyloid beta protein (A beta), which has been shown to possess ion channel activity. However, the possible role of other cleaved products of the beta APP is less clear. We have investigated the ability of various products of beta APP to induce membrane ion currents by applying them to Xenopus oocytes, a model system used extensively for investigating electrophysiological aspects of cellular, including neuronal, signalling. We focussed on the 105-amino-acid C-terminal fragment (CT105) (containing the full sequence A beta), which has previously been found to be toxic to cells, although little is known about its mode of action. We have found that CT105 is exceedingly potent, with a threshold concentration of 100-200 nM, in inducing nonselective ion currents when applied from either outside or inside the oocyte and is more effective than either beta APP or the A beta fragments, beta 25-35 or beta 1-40. The ion channel activity of CT105 was concentration dependent and blocked by a monoclonal antibody to A beta. These results suggest the possible involvement of CT105 in inducing the neural toxicity characteristic of AD.
Fraser
S P
SP
Department of Biology, Imperial College of Science, Technology and Medicine, London, England.
Suh
Y H
YH
Chong
Y H
YH
Djamgoz
M B
MB
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004553:Electric Conductivity; D005110:Extracellular Space / Q000187:drug effects; D005260:Female; D007425:Intracellular Membranes / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D014982:Xenopus laevis / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments