NEUROSTAD · Characterization of the gene and protein networks regulated by Staufen 2 in neurogenesis and their alterations in AD
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-06-01 → 2023-10-12
- EU contribution
- €172,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Characterization of the gene and protein networks regulated by Staufen 2 in neurogenesis and their alterations in AD
Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting 60% of the 55 million people with dementia globally. It leads to a gradual loss of cognitive functions, posing a significant global health challenge. One critical aspect of AD is the impact on hippocampal neurogenesis, which contributes to the progressive loss of recent memory.The urgent need to address this global health challenge posed by AD drive us to propose NEUROSTAD project, which explores the intricate world of neurogenesis. Neurogenesis is the process by which new neurons form in the brain, and we aim to decode the role of Staufen2 (STAU2) in this fundamental process, exploring its implications for AD. Deeper knowledge will help unravel the complexities of AD and other neurodegenerative diseases, paving the way for innovative treatment approaches. This increased understanding has the potential to significantly improve the healthcare system, offering enhanced prevention, accurate diagnostics, and more personalized treatment options for AD and other related disorders. The overall objectives of this Marie Skłodowska Curie Action (MSCA) have been (i) generating and analyzing the transcriptome of a STAU2 Knockout (KO) hiPSC cell line at the single-cell level during various stages of neuronal differentiation; (ii) compare the transcriptome of the STAU2 KO differentiation with the single-cell transcriptomic profiles from AD patients hiPSCs undergoing neuronal differentiation; (iii) unraveling the pivotal role of STAU2 in neurogenesis and (iv) exploring its potential implications in AD. In parallel, the goal of the MSCA Individual Fellowship is the personal growth of the Fellow towards scientific independence and to enrich the European community with excellent researchers to face the forthcoming challenges of the future.
Data: CORDIS, © European Union
Project objective
Neurogenesis is a crucial process by which new neurons are formed in the brain through the conversion of Neuronal stem cells (NPCs). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human brains and rodent models, yet the exact mechanism of the dysregulation is unknown. Over the past few years, growing evidence indicates that RNA-binding proteins (RBPs) play a critical role to fine-tune neurogenesis and mediate cortical development in the mammalian brain. Among these, the RNA-binding protein Staufen 2 (Stau2) plays an important role during neurogenesis unbalancing NSCs maintenance and differentiation, which is critical for brain development and functions. Importantly, STAU2 protein has been shown to be downregulated in AD, suggesting a possible role of STAU2 in impaired adult neurogenesis in ADIn this project, I will use induced pluripotent stem cells in combination with single-cell transcriptomic methods to characterize the unknown gene and protein networks regulated by STAU2 in neurogenesis at the single-cell level and investigate their relationship to altered neurogenesis in AD. This work will provide a solid molecular knowledge about the role of Stau2 in neural differentiation and its impact in neurogenesis in AD. Furthermore, I will develop a pipeline for the study of RBPs in human diseases and I will acquire indispensable scientific skills to become an independent research in Europe Together, this study will provide a solid molecular knowledge of the role of RBPs in neural differentiation, enabling the development of new personalized medicine therapies, which is in compliance with the Horizon H2020 Health demographic change and wellbeing program.
Original text from CORDIS.
Participants
- FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE · L'Hospitalet De LlobregatCoordinatorSpain
Links
Data: CORDIS, © European Union