HEИндивидуална стипендия2022–2025

tR-GET HD · Contribution of tRNA fragments in the ETiopathogenesis of Huntington's Disease (tR-GET HD)

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

Период: 2022-10-15 → 2025-03-14
Финансиране от ЕС: 188 122 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Фрагменти от тРНК и малки РНК молекули се анализират, за да се разбере как влияят върху развитието на болестта на Хънтингтън. Това помага за откриването на нови молекулярни механизми, които могат да бъдат използвани при разработването на бъдещи терапии.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Contribution of tRNA fragments in the ETiopathogenesis of Huntington's Disease (tR-GET HD)

Huntington’s disease (HD) is a rare but devastating inherited brain disorder that causes progressive movement, cognitive, and psychiatric symptoms. Despite decades of research, there is still no cure. It is known that HD results from a genetic mutation leading to the production of an abnormal form of a protein called huntingtin, but the precise molecular mechanisms driving these events remain unclear. This project explores how small RNAs and other pathogenic processes might influence the development of HD. Recent discoveries suggest that these molecules and cellular responses could be linked to HD-related neurotoxicity. By investigating their roles in disease progression, the research aims to uncover new molecular mechanisms that could be targeted for therapy. The work brings together complementary expertise in RNA biology, brain toxicity, and neurodegenerative disease models. Using a range of experimental and computational approaches, the project seeks to identify early changes in HD at the molecular level and evaluate potential strategies to counteract them. Beyond advancing scientific understanding, the project will strengthen collaborations between leading European neuroscientists and support the researcher’s growth as an independent investigator in neurodegenerative disease research. The ultimate goal is to contribute to the discovery of new, RNA-based therapeutic approaches that may one day benefit people living with Huntington’s disease.

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

Цел на проекта

Many pathogenic mechanisms are involved in Huntington’s disease (HD), the most prevalent monogenic neurological disease in Europe, with no current cure. The host team reported a dysregulation of tRNA-fragments (tRFs) in HD brains; other studies showed higher stress granules' (SG) density in HD, and that tRFs promote SG assembly. Thus, my hypothesis is that HD-related tRFs contribute to the accumulation of SG, initiating mutant huntingtin (mtHTT) aggregation and leading to disease pathogenesis. I propose to explore the interaction between mtHTT aggregates, and tRFs and SG, as new potential therapeutic targets. Specifically, I aim to study the 1) cell-type specificity of tRFs formation and their correlation with HD progression; 2) molecular mechanisms by which tRFs may induce HD pathology; and 3) potential of tRFs modulators to treat mtHTT-related neurotoxicity.This project’s success relies on the perfect synergy of the host team’s expertise in tRFs biology and HD and my own experience in RNA and proteotoxicity in neurodegenerative diseases, thoroughly addressing the hypothesis via complementary human, cellular and mice HD models and a plural array of bioinformatic, molecular biology and genomic approaches. The outcomes will help define the role of tRFs and SG in mtHTT aggregation, and may be used as preclinical proof-of-concept for novel HD therapies, reflecting the project’s translational potential.I will benefit from scientific exchanges with expert neuroscientists in the host institution, particularly my supervisor, whose skills in functional genomics fully match my expertise in RNA and protein pathological mechanisms. My translational technical knowledge and network of collaborators will be useful to the host group to build new cooperative projects. Thus, the MSCA fellowships will allow me to develop unique technical and transferable skills, helping me progress and establish myself as a leader in neurodegenerative research within a European research institute.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT DE BARCELONA · BarcelonaКоординаторИспания