MECHAGGRENAMICS · Mechanisms of cell dysfunction by aggregation dynamics of polyQ-containing proteins
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-11-01 → 2016-10-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите на натрупване на вредни протеини и РНК се анализират чрез модели на болестта на Хънтингтън. Това помага да се разбере как генетичният фон влияе върху развитието на заболяването и кои лекарства могат да защитят невроните.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Mechanisms of cell dysfunction by aggregation dynamics of polyQ-containing proteins
Protein aggregation is a typical trait of a number of neurodegenerative diseases associated with aging. The genes responsible for modulating the aggregation are not completely known. There is an inverse correlation between the number of the CAG triplets within the huntingtin gene, and the age of onset of symptoms in patients of Huntington's disease (HD). However, there is a wide variation in age of onset of the disease, among carriers of short but toxic CAG tandems, which suggests that the genetic background of the patients strongly influences the severity of the disease. In this proposal we have generate new in vivo models of HD to find molecules that modulate protein and RNA toxicity and disease progression. We also have tested several compound that reduce aggregation patterns, and also induce neuronal protection in contexes of polyQ toxicity. We have found seeveral genes involved in protein toxicity dynamics, and also in genes that are involved in the toxicity produced by the nascent RNA containing expanded CAG triplets. We are currently testing drugs against HD in a mice model of HD, the so-called zQ175. Some of these compounds will be considered for future clinical trials. More information at the website of our lab: www.biomcg-wormlab.org
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Protein aggregation is a hallmark of several ageing-related neurodegenerative diseases, such as Huntington’s disease (HD), Alzheimer’s disease and prion-mediated diseases. Different cellular pathways influence the rate of aggregation, and clearance of intermediate protein species and aggregates in the cell (for example, autophagy or proteasomal degradation). Many signalling pathways regulate these processes. These signalling events, and the molecular pathways downstream are not completely understood. In HD there is an inverse correlation between the number of CAG triplets found in mutated huntingtin (htt) and the age-of-onset of the symptoms. However, there is a wide variation in the age-at-onset of the disease among carriers of short mutant glutamine tracts, suggesting that the genetic background strongly influences the severity of the disease. Hence the broad objective of this proposal is to find molecules that modulate protein aggregation.We will use in vivo (C. elegans) and in vitro (mammalian cells) models of HD to find new molecules and pathways that modulate aggregation and toxicity induced by polyglutamines. The second objective of this proposal is to understand the mechanism by which mHtt toxic species alter cellular processes, with special focus on pre-synaptic function.
Оригинален текст от CORDIS (на английски).
Участници
- FUNDACION PARA LA INVESTIGACION DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA · ValenciaКоординаторИспания
Връзки
Данни: CORDIS, © Европейски съюз