NCRNANEURO · Non-coding RNAs in neurodegeneration
FP7 — People (Marie Curie Actions)
- Duration
- 2010-10-01 → 2012-09-30
- EU contribution
- €214,800
- Participants
- 1
- Scheme
- MC-IIF
Lines connect the coordinator with its partners.
Results in brief
Non-coding RNAs in neurodegeneration
The main goal: The goal of the project 'Non-coding RNAs in neurodegeneration' was to find differentially expressed microRNAs in the brains of Alzheimer's Disease patients. We obtained 49 human brain samples from the Netherlands and 64 additional samples from England. The Dutch cohort corresponded to 7 prefrontal cortex samples belonging to each of the 6 Braak stages and to 7 additional controls. The English cohort was made of hippocampal samples from 23 controls and 42 late-onset Alzheimer's Disease patients. The main result: Profiling of miRNAs in the prefrontal cortex of the Dutch cohort using the nCounter multiplexing technology and time-course analysis showed expression changes of 33 miRNAs starting at early Braak stages, therefore showing that deregulation of miRNAs was not a passive consequence and late event during the disease. In the hippocampus, we found 38 miRNAs deregulated, allowing a classification of these sporadic cases at high accuracy and specificity. After intersection of the two datasets and validation by real-time PCR, we identified four miRNAs including miR-132, -129-5p, -136 and -92b as being consistently altered between controls and Alzheimer's Disease patients. Our result unequivocally demonstrated a down-regulation of miR-132 in neurons of Alzheimer's Disease patients showing Tau hyperphosphorylation and we further provided evidence that down-regulation of miR-132 may contribute to disease progression partially through aberrant expression of mRNA targets found in the Tau pathway. Conclusions and socio-economic impacts of the project: MicroRNAs are regarded as potential biomarkers of disease. We found 4 miRNAs that could represent specific markers of Alzheimer's Disease or of neurodegenerative disorders. This study adds an additional tool for the clinical detection of Alzheimer's Disease together with pre-established biomarkers of the disease such as amyloid beta and hyperphosphorylated Tau.
Data: CORDIS, © European Union
Project objective
Large non-coding RNAs and microRNAs are important regulators of gene expression that may control both physiological and pathological processes such as neurodegenerative disorders. Given the complexity of neurodegenerative disorders, studying the role of non-coding RNAs would be necessary to understand the molecular mechanisms underlying ageing related neurodegeneration. Of particular interest, microRNAs (miRNAs) seem to participate directly in the regulation of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) related genes. In this regard, microRNA research would be promising for the understanding of the very prevalent and poorly understood sporadic forms of AD and possibly PD. To address the role of specific microRNAs in biological models, the project will consist in determining whether down-regulation of specific microRNAs in zebrafish and mouse models recapitulate neurodegeneration. The identification of mRNA targets of such microRNAs will provide insight into the cellular pathways that are disturbed after microRNA knock-down. To complement the study on microRNAs, another objective of the project will be to determine whether large non-coding RNAs are dysregulated in neurodegenerative diseases similar to what is observed for microRNAs. The study of non-coding RNAs will provide a novel layer of complexity in neuronal cell biology and be exciting tools to probe and discover molecular mechanisms underlying neurodegeneration.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union