HEИндивидуална стипендия2023–2025

NeuProHRI · NeuroProtective role of HRI following cerebral ischemia

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

Период: 2023-06-01 → 2025-05-31
Финансиране от ЕС: 165 313 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на протеина HRI се изследва чрез опити с неврони и мишки, за да се разбере как той защитава мозъка след инсулт. Това е важно, защото липсата на надеждни методи за лечение прави търсенето на нови терапевтични цели приоритет.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

NeuroProtective role of HRI following cerebral ischemia

Nowadays, cerebrovascular diseases are devastating conditions representing a large cause of mortality worldwide. It is estimated that 1.1 million people suffer a stroke every year in Europe. Due to the lack of a reliable treatment for stroke, it is important to keep looking for new treatments that stop the progression of the insult by providing neuroprotection, and even promote neuronal recovery for those neurons already affected by the condition. The goal of NeuProHRI is to study the potential of targeting the HRI kinase cellular cascade as a new therapeutic aim for stroke. To develop this, a combination of cutting-edge molecular techniques will be used to define the cellular pathways underlying the activation of the HRI kinase, and their effect on promoting neuroprotection in in vitro and in vivo models of stroke. First, molecular cascade will be deciphered following the activation of HRI in primary cultured neurons by pharmacological and genetic approaches. Then, in vitro models of stroke will be used to measure the impact of these treatments in cells with stroke-like phenotype. Finally, mouse models of stroke will allow to tackle the impact of pharmaceutical and genetic treatments on in vivo brain tissue. Considering the aforementioned background, the overall objective of NeuProHRI is to deciphering the cellular pathway underlying HRI-induced eIF2α phosphorylation in healthy and stressed cells after ischemia; as well as its in vivo role as therapeutic target in mouse models of IS. Therefore, 3 specific objectives are proposed: 1. Identifying all players participating in the downstream signaling following HRI activation. 2. HRI as a potential therapeutic target for IS. 3. Determining the impact of HRI-induced eIF2α phosphorylation on mRNA translation in vivo after IS.

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

Цел на проекта

Nowadays, cerebrovascular diseases are devastating conditions representing a large cause of mortality worldwide. It is estimated that 1.1 million people suffer a stroke every year in Europe. Due to the lack of a reliable treatment for stroke, it is important to keep looking for new treatments that stop the progression of the insult by providing neuroprotection, and even promote neuronal recovery for those neurons already affected by the condition. The goal of NeuProHRI is to study the potential of targeting the HRI kinase cellular cascade as a new therapeutic aim for stroke. To develop this, I will use a combination of cutting-edge molecular techniques to define the cellular pathways underlying the activation of the HRI kinase, and their effect on promoting neuroprotection in in vitro and in vivo models of stroke. First, I will decipher the molecular cascade following the activation of HRI in primary cultured neurons by pharmacological and genetic approaches. Then, in vitro models of stroke will be used to measure the impact of these treatments in cells with stroke-like phenotype. Finally, mouse models of stroke will allow me to tackle the impact of pharmaceutical and genetic treatments on in vivo brain tissue. Moreover, Ribo-seq analysis will be performed to study accurately protein synthesis and its relation to neuron-intrinsic pathways involved in stroke. There is a clear benefit of the mobility for both the applicant and the host, ensuring high quality results and dissemination. In this regard, the host will ensure the acquisition of new technical, management, tutorial and transferable skills. The applicant will also benefit from a multidisciplinary environment enhancing international collaboration that will surely contribute to diversify his career. Finally, via a specialized Career Development Plan, the host will provide the ideal training and validation environment, through which the applicant will reach unprecedented levels of professional maturity.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACION PUBLICA GALEGA INSTITUTO DE INVESTIGACION SANITARIA DE SANTIAGO DE COMPOSTELA · Santiago De CompostelaКоординаторИспания
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisФранция