Project description
Epigenetics as a key driver of Parkinson’s disease
Epigenetic modifications such as methylation are well known to impact gene expression. Accumulating evidence indicates that N6-methyladenosine (m6A) methylation of eukaryotic RNAs serves as a post-transcriptional regulatory marker affecting splicing, translation and stability. Moreover, there has been a direct link with decreased m6A methylation and neuronal apoptosis. Funded by the Marie Skłodowska-Curie Actions programme, the PARTHECOM project aims to investigate how m6A regulates dopamine neuron survival and axonal regeneration. Researchers will identify which mRNAs with altered m6A methylation are responsible for dopamine neuron survival and test various small neuroprotective molecules. The work is expected to open new directions in research on Parkinson’s disease where dopamine neurons play a key role.
Objective
Parkinson’s disease (PD) is a neurodegenerative disease with growing incidence. More than 10 million people worldwide are affected by this condition. In addition to decline in the patients’ quality of life, the economic burden of PD is estimated to exceed 13,9 billion EUR in EU annually. Considering this, novel and more efficient therapeutic options are needed, as current PD treatments alleviate symptoms without stopping neurodegeneration and progression of the disease. Although the etiology of PD is unclear, degeneration of dopamine (DA) neurons has been shown to result from certain genetic mutations, toxins and pathological protein aggregation among others. Importantly, recent evidence points to decrease in mRNA methylation at adenosine N6 (m6A) in PD. Data also indicate that m6A reduction may induce DA neuron apoptosis.
Prof. Mart Saarma and collaborators have discovered that m6A methylation is a crucial regulator of neuronal apoptosis. They developed novel m6A methyltransferase activators and demethylase inhibitors that potently enhance mRNA m6A levels. Importantly, preliminary data show that these compounds protect DA neurons from neurotoxin-induced death in culture at nanomolar concentration. Moreover, one compound tested thus far remarkably improves motor behavior, protects and regenerates DA neurons and their axons in rat PD model more potently than “gold standard” GDNF. Considering this, the current project aims to elucidate the mechanisms how m6A regulates DA neuron survival and axonal regeneration. We will identify for the first time the mRNAs with increased/decreased methylation at adenosine N6 that regulate the life and death of DA neurons, thereby potentially opening new directions in PD research. In addition, we aim to provide completely new lead molecules for PD treatment.
In conclusion, the current project aims to broaden our understanding on the mechanisms of Parkinson’s disease and provide new drug candidates for novel PD therapeutic avenues.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
00014 HELSINGIN YLIOPISTO
Finland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.