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

Projektinformationen

toxiclipasyn

ID Finanzhilfevereinbarung: 706551

DOI

10.3030/706551

Das Projekt endete am 31 März 2019

EK-Unterschriftsdatum 8 November 2016

Startdatum 1 Mai 2017

Enddatum 30 April 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 171 460,80

EU-Beitrag

€ 171 460,80

Koordiniert durch

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)

Berichtszeitraum: 2017-05-01 bis 2019-04-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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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