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Alzheimer's: Structural properties of complex model membranes after interaction with beta-amyloid peptides open the way to the identification of new drug targets

Date:
June 13, 2016
Source:
Università degli Studi di Milano
Summary:
A new report describes the structural properties of complex model membranes after the interaction with beta-amyloid peptides, involved in Alzheimer's disease, opening the way to the identification of new drug targets.
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Scientific Reports publishes a study of BIOMETRA department researchers on the structural properties of complex model membranes after the interaction with β-amyloid peptides, involved in Alzheimer disease, opening the way to the identification of new drug targets.

A collaboration between the department of Medical Biotechnologies and Translational Medicine at the University of Milano, the department of Molecular Biochemistry and Pharmacology at the Institut for Pharmacological Research Mario Negri in Milano and the Institut Laue-Langevin (ILL) in Grenoble, revealed the existence and extent of interaction between different Aβ(1-42) peptides and single complex biomimetic membranes. The membrane, asymmetrically containing phospholipids, GM1 and cholesterol in biosimilar proportion, is a model for a raft, a putative site for amyloid-cell membrane interaction. Neutron reflectivity experiments revealed that the interaction with membranes depends on peptide aggregative state.

The research reveals that the structured-oligomer of Aβ(1-42), its most acknowledged membrane-active state, is embedded as such into the external leaflet of the membrane. Conversely, the Aβ(1-42) unstructured early-oligomers deeply penetrate the membrane, likely mimicking the interaction at neuronal cell surfaces, when the Aβ(1-42) is cleaved from APP protein (Amyloid Precursor Protein) and the membrane constitutes a template for its further structural evolution. Moreover, the smaller Aβ(1-6) fragment, the N-terminal portion of Aβ, was also used. Aβ N-terminal is usually considered as involved in oligomer stabilization but not in the peptide-membrane interaction. Instead, it was seen to remove lipids from the bilayer, thus suggesting its role, once in the whole peptide, in membrane leakage, favouring peptide recruitment.

Together with the known ability of seeds, formed by small peptide aggregates, in driving Aβ recruitment towards fiber formation, this new vision potentially enables us to identify new drug targets.

Given over 9.9 million new cases of dementia are appearing each year worldwide, furthering research into Alzheimer's Disease has never been more important. The aims of the study therefore highlight the impact of developing synergistic interdisciplinary research collaborations.


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Materials provided by Università degli Studi di Milano. Note: Content may be edited for style and length.


Journal Reference:

  1. Valeria Rondelli, Paola Brocca, Simona Motta, Massimo Messa, Laura Colombo, Mario Salmona, Giovanna Fragneto, Laura Cantù, Elena Del Favero. Amyloidβ Peptides in interaction with raft-mime model membranes: a neutron reflectivity insight. Scientific Reports, 2016; 6: 20997 DOI: 10.1038/srep20997

Cite This Page:

Università degli Studi di Milano. "Alzheimer's: Structural properties of complex model membranes after interaction with beta-amyloid peptides open the way to the identification of new drug targets." ScienceDaily. ScienceDaily, 13 June 2016. <www.sciencedaily.com/releases/2016/06/160613090719.htm>.
Università degli Studi di Milano. (2016, June 13). Alzheimer's: Structural properties of complex model membranes after interaction with beta-amyloid peptides open the way to the identification of new drug targets. ScienceDaily. Retrieved May 24, 2017 from www.sciencedaily.com/releases/2016/06/160613090719.htm
Università degli Studi di Milano. "Alzheimer's: Structural properties of complex model membranes after interaction with beta-amyloid peptides open the way to the identification of new drug targets." ScienceDaily. www.sciencedaily.com/releases/2016/06/160613090719.htm (accessed May 24, 2017).

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