H2020Индивидуална стипендия2017–2019

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-05-01 → 2019-04-30
Финансиране от ЕС: 171 461 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействието между протеина алфа-синуклеин и мазнините в клетъчните мембрани определя дали той ще помогне за комуникацията между невроните или ще образува вредни струпвания. Разбирането на този процес помага да се разберат причините за развитието на болестта на Паркинсон.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Proteins are among the most essential molecules of life. In order to fulfil their native function(s) they need to adopt a well-defined three-dimensional structure. However, under some circumstances, proteins can misfold and/or form toxic amyloid structures, which are the hallmark of a range of diseases including type 2 diabetes and neurodegenerative diseases. In particular, the small pre-synaptic protein, alpha-synuclein (AS), whose aggregation is the hallmark of Parkinson’s disease, can adopt in vivo and in vitro an intrinsically disordered conformation in solution and an alpha helical state when bound to membranes; the equilibrium between these two conformations has been shown to be important for its proposed native function, e.g. synaptic plasticity, and to modulate its kinetics of fibril formation. Here, I propose to investigate the physiological factors responsible for the switch between functional and deleterious interactions between membrane bilayers and AS due to ageing or disease using an innovative combination of biological, structural, thermodynamic and kinetic studies. In particular, I propose to use both synthetic lipid model systems and isolated synaptic vesicles to study the effect of ageing and the presence of lipids associated with Parkinson’s disease pathology on the nature of the interaction between AS and lipid bilayers. The synaptic vesicles will be isolated from the brain of mice at different ageing stages, as well as from mice carrying gene modifications or knock out related to PD. The interaction between AS and the vesicles will be studied using a range of biophysical techniques including circular dichroism, fluorescence and nuclear magnetic resonance spectroscopy, Atomic Force and Electron Microscopy.The aim of this study is to establish a thorough understanding of the interplay between changes in lipid composition and increased propensity of protein aggregation.

Оригинален текст от CORDIS (на английски).

Участници

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV · BonnКоординаторГермания