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OsteoCalcin Autophagy to reJuvenate motoneuronAL function

Project description

Investigating the role of osteocalcin in locomotor functions

Recent studies have demonstrated that several organs impact brain ageing. The bone-derived hormone osteocalcin (Ocn) was identified as a rejuvenating systemic factor improving memory in aged mice. The EU-funded CAJAL project aims to understand the rejuvenating role of Ocn in age-related motoneuron (MN) and locomotor dysfunctions. The Ocn receptor is present in spinal MNs, and Ocn influences MN autophagy, which is essential for locomotor performance. The project’s objective is to elucidate the potential protective role of Ocn-autophagy in MNs’ maintaining locomotor activity. By achieving this, CAJAL could lead to new therapies for age-related locomotor system decline.

Objective

Brain aging is characterized by a progressive decline of our nervous system functions. Elucidating the underlying mechanisms is of vital importance and represents an unmet medical need. Recent studies have highlighted the molecular contribution of several organs in brain aging, and emphasize the importance of systemic milieu in the control of cognitive fitness. Host has identified Osteocalcin (Ocn), a bone-derived hormone, as a rejuvenating systemic factor that improves memory in aged-mice. However, the impact of systemic factors in our locomotor functions and their therapeutic potential remain unexplored.

CAJAL aims to elucidate the role of the pro-rejuvenating hormone Ocn in the age-related motoneuron (MN) and locomotor dysfunctions. Our preliminary data show that Ocn receptor is highly expressed in spinal MNs and that Ocn influences MN autophagy, an essential endogenous mechanism for locomotor performance. We propose to analyse the potential protective role of Ocn-autophagy in MNs to maintain locomotor activity. By shedding light on key molecular mechanisms fostering MN homeostasis, CAJAL could lead to new therapeutic strategies to treat/prevent age-related decline of locomotor system.

The specific objectives are:
1) Characterize the impact of systemic milieu/Ocn in regulating autophagy in spinal MNs
2) Analyze the therapeutic potential of Ocn in age-related locomotor decline
3) Decipher the role of Ocn-dependent autophagy in locomotor function and its signalling pathway

The project is designed to extend my scientific expertise and transfer my knowledge in autophagy and MN homeostasis to Host. Project and risk management, intellectual property rights, and communication activities are meticulously planned.
We have generated the required molecular tools and mouse models, as well as strong collaborations with international experts in autophagy, neuroendocrinology and aging. Supervisor experience together with INEM represent the best environment to develop CAJAL.

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Keywords

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Programme(s)

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Topic(s)

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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.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2020

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

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.

€ 184 707,84
Total cost

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.

€ 184 707,84
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