Apoptosis induced in neuronal cells by C-terminal amyloid beta-fragments is correlated with their aggregation properties in phospholipid membranes

Citation
N. Demeester et al., Apoptosis induced in neuronal cells by C-terminal amyloid beta-fragments is correlated with their aggregation properties in phospholipid membranes, MOL MEMBR B, 17(4), 2000, pp. 219-228
Citations number
60
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR MEMBRANE BIOLOGY
ISSN journal
09687688 → ACNP
Volume
17
Issue
4
Year of publication
2000
Pages
219 - 228
Database
ISI
SICI code
0968-7688(200010/12)17:4<219:AIINCB>2.0.ZU;2-W
Abstract
A number of findings suggest that lipophilic monomeric A beta peptides can interact with the cellular lipid membranes. These interactions can affect t he membrane integrity and result in the initiation of apoptotic cell death. The secondary structure of C-terminal A beta peptides (29-40) and the long er (29-42) variant have been investigated in solution by circular dichroism measurements. The secondary structure of lipid bound A beta (29-40) and (2 9-42) peptides prepared at different lipid/peptide ratio's, was Investigate d by ATR-FTIR spectroscopy. Finally, the changes in secondary structure (i. e. the transition of alpha -helix to beta -sheet) of the lipid bound peptid es were correlated with the induction of neurotoxic and apoptotic effects i n neuronal cells. The data suggest that the C-terminal fragments of the A b eta peptide induce a significant apoptotic cell death, as demonstrated by c aspase-3 measurements and DNA laddering, with consistently a stronger effec t of the longer A beta (29-42) variant. Moreover, the induction of apoptoti c death induced by these peptides can be correlated with the secondary stru cture of the lipid bound amyloid beta peptides, eased on these observations , if is proposed that membrane bound aggregated A beta peptides (produced l ocally as the result of gamma -secretase cleavage) can accumulate and aggre gate in the membrane. These membrane bound beta -sheet aggregated amyloid p eptides induce neuronal apoptotic cell death.