Understanding the balance between functional and deleterious interactions of alpha-synuclein with lipid bilayers

Informations projet

toxiclipasyn

N° de convention de subvention: 706551

DOI

10.3030/706551

Projet clôturé le 31 Mars 2019

Date de signature de la CE 8 Novembre 2016

Date de début 1 Mai 2017

Date de fin 30 Avril 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 171 460,80

Contribution de l’UE

€ 171 460,80

Coordonné par

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Germany

Periodic Reporting for period 1 - toxiclipasyn (Understanding the balance between functional and deleterious interactions of alpha-synuclein with lipid bilayers)

Période du rapport: 2017-05-01 au 2019-04-30

Résumé du contexte et des objectifs généraux du projet

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder at older age causing disability and care dependency. In 2016, more than six million people were diagnosed with PD and this number is expected to increase by 92% over the next 40 years. Such an increase in the number of patients will lead to significant social and financial burden on our ageing societies.

PD is characterized by the deposition of protein clumps called Lewy Bodies (LB) and Lewy neurites (LN) in the brain of patients. LB and LN are mainly composed of the protein alpha-synuclein but can also contain lipid (fat) molecules, the main constituents of biological membrane. A-synuclein interacts with membranes as part of its functional role, i.e. to help neurons to communicate with one another, but alpha-synuclein also form clumps in their presence. Indeed, the nature of lipids in membrane dictates whether or not alpha-synuclein is functional or can form clumps.

This action aimed at identifying changes in lipid levels and/ or properties associated with PD and determining their influence on the propensity of alpha-synuclein to form clumps.

The aims of this action were overall successfully addressed.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During the course of this action, biological membranes were isolated from different animal and cellular models of PD. Their lipid composition was determined and the extent to which they were able to initiate the formation of clumps by alpha-synuclein was investigated.

The results of this action allowed the identification of a list of lipids whose levels and properties affect alpha-synuclein aggregation under pathophysiologically relevant conditions. In particular, data support the concept that PD risk factors may act by changing cellular lipid profiles and thus promoting the formation of alpha-synuclein clumps.

These results are currently described in a manuscript in preparation for publication. Once published, these results will be presented in conferences targeted at scientists in the field of neuroscience, lipid metabolism and protein aggregation.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The results provide new insights into the role of lipids in the pathogenesis of PD and support a role of lipid-alpha-synuclein interactions as a mechanism of increased PD risk. They also have the potential to help the development of new diagnostic tools and pharmaceutical treatments.

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