Apoptotic neuronal cell death induced by the non-fibrillar amyloid-beta peptide proceeds through an early reactive oxygen species-dependent cytoskeleton perturbation - PubMed (original) (raw)

. 2003 Jan 31;278(5):3437-45.

doi: 10.1074/jbc.M206745200. Epub 2002 Nov 14.

Affiliations

Free article

Apoptotic neuronal cell death induced by the non-fibrillar amyloid-beta peptide proceeds through an early reactive oxygen species-dependent cytoskeleton perturbation

Isabelle Sponne et al. J Biol Chem. 2003.

Free article

Abstract

In the present study, we have determined the nature and the kinetics of the cellular events triggered by the exposure of cells to non-fibrillar amyloid-beta peptide (A beta). When cortical neurons were treated with low concentrations of soluble A beta (1-40), an early reactive oxygen species (ROS)-dependent cytoskeleton disruption precedes caspase activation. Indeed, caspase activation and neuronal cell death were prevented by the microtubule-stabilizing drug taxol. A perturbation of the microtubule network was noticeable after being exposed to A beta for 1 h, as revealed by electron microscopy and immunocytochemistry. Microtubule disruption and neuronal cell death induced by A beta were inhibited in the presence of antioxidant molecules, such as probucol. These data highlight the critical role of ROS production in A beta-mediated cytoskeleton disruption and neuronal cell death. Finally, using FRAP (fluorescence recovery after photo bleaching) analysis, we observed a time-dependent biphasic modification of plasma membrane fluidity, as early as microtubule disorganization. Interestingly, molecules that inhibited neurotubule perturbation and cell death did not affect the membrane destabilizing properties of A beta, suggesting that the lipid phase of the plasma membrane might represent the earliest target for A beta. Altogether our results convey the idea that upon interaction with the plasma membrane, the non-fibrillar A beta induces a rapid ROS-dependent disorganization of the cytoskeleton, which results in apoptosis.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources