Role of the membranair GxxxG motifs in the oligomerization and toxicity of the beta-amyloid peptide
(2012) EURON PhD student meeting — Location: Maastricht (Holland) (2012)
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- Abstract
- Alzheimer’s disease is a neurodegenerative disease that causes progressive loss of cognitive functions, leading the patient to dementia. Two types of lesions appear in the brain: neurofibrillary tangles and senile plaques. These are composed mainly of β-amyloid peptide (Aβ) that derives from a precursor, the Amyloid Precursor Protein (APP). Aβ exists under different forms: monomeric, oligomeric or fibrillar. Recent datas indicate that the oligomeric form of Aβ induces neurodegeneration and a loss of neuronal functions. The aim of the project is to study the mechanisms involved in Aβ oligomers’ formation and their toxic properties. APP possesses particular motifs in its membrane-anchored Aβ sequence: GxxxG and GxxxG-like motifs. These motifs are involved in the dimerization of membrane helices. Detailed analysis of this region and our recent work indicate that these two patterns (GxxxG and GxxxA) would control the formation of oligomeric Aβ in membranes. We are actually studying the mechanisms underlying the formation of these oligomers by a site-directed mutagenesis approach. Expression of those mutants in CHO cells revealed that some of them displayed dramatic changes in the Aβ oligomerization profile. We are also analyzing their localization in the cell and their toxic properties in vitro and in vivo by injecting mice brains with AAVs.
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Citations
Decock, M., Marinangeli, C., Stancu, I.-C., Stanga, S., Dewachter, I., Octave, J.-N., & Kienlen-Campard, P. (2012). Role of the membranair GxxxG motifs in the oligomerization and toxicity of the beta-amyloid peptide. EURON PhD student meeting, Maastricht (Holland). https://hdl.handle.net/2078.5/201201