LPYFDa neutralizes amyloid-beta-induced memory impairment and toxicity.
Misfolding, oligomerization, and aggregation of the amyloid-beta (Abeta) peptide is widely recognized as a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies have identified soluble Abeta oligomers as the main pathogenic agents and provided evidence that such oligomeric Abeta aggregates are neurotoxic, disrupt synaptic plasticity, and inhibit long-term potentiation. A promising therapeutic strategy in the battle against AD is the application of short synthetic peptides which are designed to bind to specific Abeta-regions thereby neutralizing or interfering with the devastating properties of oligomeric Abeta species. In the present study, we investigated the neuroprotective properties of the amyloid sequence derived pentapeptide LPYFDa in vitro as well as its memory preserving capacity against Abeta(42)-induced learning deficits in vivo. In vitro we showed that neurons in culture treated with LPYFDa are protected against Abeta (42) -induced cell death. Moreover, in vivo LPYFDa prevented memory impairment tested in a contextual fear conditioning paradigm in mice after bilateral intrahippocampal Abeta (42) injections. We thus showed for the first time that an anti-amyloid peptide like LPYFDa can preserve memory by reverting Abeta (42) oligomer-induced learning deficits.
Department of Molecular Neurobiology, University of Groningen, Haren, The Netherlands.
Ivica
I
Granic
Marcelo F
MF
Masman
Cornelis
C
Kees Mulder
Ingrid M
IM
Nijholt
Pieter J W
PJ
Naude
Ammerins
A
de Haan
Emöke
E
Borbély
Botond
B
Penke
Paul G M
PG
Luiten
Ulrich L M
UL
Eisel
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004586:Electrophoresis; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D009842:Oligopeptides; C539346:leucyl-prolyl-tyrosyl-phenylalanyl-aspartamide