H2020Индивидуална стипендия2016–2018

HEALTHYSYNAPSES · Molecular mechanisms underlying synaptic maintenance and rejuvenation

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

Период: 2016-03-01 → 2018-02-28
Финансиране от ЕС: 160 800 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Синаптичната автофагия изследва как мозъкът почиства повредените протеини в връзките между невроните, за да поддържа тяхната функция. Разбирането на тези процеси помага при търсенето на начини за справяне с дегенеративни заболявания като деменция и болест 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

Molecular mechanisms underlying synaptic maintenance and rejuvenation

Diseases of the brain like dementias and other neurodegenerative conditions (for e.g. Parkinson's) are becoming a more prevalent aspect of our society. As our lifespan increases, the prevalence is only going to increase. So it has become crucial that we understand the mechanisms that are affected in brain disorders and explore means by which we may be able to tackle these disorders by reducing or eliminating their degenerative effects. Within the brain, it has become clear that proper function depends on the fidelity of synaptic transmission. Furthermore, the failure of synapses is an early and key phenomenon in neurodegenerative disorders. Therefore, I am interested in understanding how accurate synaptic function is maintained throughout lifetime. My interest was focused on the maintenance of protein homeostasis at the synapse through the process of autophagy – a group of cellular mechanisms that are involved in the degradation of dysfunctional proteins and other cytoplasmic entities. I wanted to develop the links between autophagy and neuronal function. I wanted to see whether changes in autophagy could be linked to the dysfunction seen at synapses and all the associated phenotypes seen in the brain during ageing and disease conditions. I was also interested in identifying the specific autophagic pathways active at the synapse and to identify synaptic proteins that has unique roles in modifying synaptic autophagy. Furthermore, I wanted to generate tools that could help us study and control autophagy at the synapse with precision. I believe that the better understanding of synaptic autophagy that we have gained from this project will help us harness the power of autophagy as a therapeutic means of maintaining synaptic function and potentially restoring altered synaptic function in disease conditions.

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

Цел на проекта

The deterioration of brain function and prevalence of dementias are some of the most striking and unfortunate consequences of ageing. Proper neuronal function relies on accurate signal transmission via synapses. While the basic cell biology of synaptic transmission is well studied, how precise activity is maintained over time remains poorly understood. Several age-dependent neurodegenerative conditions, characterized by the build-up of protein aggregates, affect synaptic function. These observations are consistent with a model where defects in the repair mechanisms that clear away defective proteins may constitute the basis for synaptic dysfunction and neurodegeneration. However, the processes that control protein rejuvenation at the synapse remain elusive. Autophagy is a process that is well suited for this purpose as it has emerged as a major means by which the cell can degrade dysfunctional components but a specific role for autophagy at the synapse has not been established. Levels in autophagy have been strongly linked to longevity and neuronal health. I hypothesize that autophagy plays an important role in synapse maintenance and that synaptic autophagy is disrupted during ageing and in neurodegenerative diseases. I will utilize a diverse set of approaches to elucidate the link between autophagy and changes in synaptic function during ageing in Drosophila. By generating novel optogenetic tools, I propose to test how the precise modulation of autophagy can influence synaptic function and whether boosting synaptic autophagy is beneficial in ageing and disease conditions. Furthermore, I will conduct a large-scale genetic screen for identifying genes regulating synaptic autophagy. Finally, I will explore the intriguing connections between synaptic proteins implicated in Parkinson’s disease and autophagy. Revealing the mechanisms underlying synaptic maintenance and health will help guide strategies for alleviating the undesirable effects of ageing.

Оригинален текст от CORDIS (на английски).

Участници

VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия