Biochim Biophys Acta  2003 Jan 10;1609(1):28-38 

Piracetam inhibits the lipid-destabilising effect of the amyloid peptide Abeta
C-terminal fragment.

Mingeot-Leclercq MP, Lins L, Bensliman M, Thomas A, Van Bambeke F, Peuvot J,
Schanck A, Brasseur R.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite catholique de
Louvain, Brussels, Belgium.

Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor
protein (APP), implicated in the pathogenesis of Alzheimer's disease. The
hypothesis that interactions between Abeta aggregates and neuronal membranes
play an important role in toxicity has gained some acceptance. Previously, we
showed that the C-terminal domain (e.g. amino acids 29-42) of Abeta induces
membrane permeabilisation and fusion, an effect which is related to the
appearance of non-bilayer structures. Conformational studies showed that this
peptide has properties similar to those of the fusion peptide of viral proteins
i.e. a tilted penetration into membranes. Since piracetam interacts with lipids
and has beneficial effects on several symptoms of Alzheimer's disease, we
investigated in model membranes the ability of piracetam to hinder the
destabilising effect of the Abeta 29-42 peptide. Using fluorescence studies and
31P and 2H NMR spectroscopy, we have shown that piracetam was able to
significantly decrease the fusogenic and destabilising effect of Abeta 29-42, in
a concentration-dependent manner. While the peptide induced lipid
disorganisation and subsequent negative curvature at the membrane-water
interface, the conformational analysis showed that piracetam, when preincubated
with lipids, coats the phospholipid headgroups. Calculations suggest that this
prevents appearance of the peptide-induced curvature. In addition, insertion of
molecules with an inverted cone shape, like piracetam, into the outer membrane
leaflet should make the formation of such structures energetically less
favourable and therefore decrease the likelihood of membrane fusion.

PMID: 12507755 [PubMed - indexed for MEDLINE]