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

Informazioni relative al progetto

toxiclipasyn

ID dell’accordo di sovvenzione: 706551

DOI

10.3030/706551

Progetto concluso il 31 Marzo 2019

Data della firma CE 8 Novembre 2016

Data di avvio 1 Maggio 2017

Data di completamento 30 Aprile 2019

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 171 460,80

Contributo UE

€ 171 460,80

Coordinato da

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)

Periodo di rendicontazione: 2017-05-01 al 2019-04-30

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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