OsteoCalcin Autophagy to reJuvenate motoneuronAL function

Descripción del proyecto

Investigar la función de la osteocalcina en las funciones locomotoras

Estudios recientes han demostrado que varios órganos afectan al envejecimiento del encéfalo. La hormona derivada del hueso osteocalcina (Ocn) fue identificada como un factor sistémico rejuvenecedor que mejora la memoria en ratones viejos. El proyecto financiado con fondos europeos CAJAL pretende comprender el papel rejuvenecedor de la Ocn en las disfunciones locomotoras y de las motoneuronas (MN) seniles. El receptor de la Ocn está presente en las MN de la médula espinal y la Ocn influye en la autofagia de las MN, que es fundamental para el rendimiento locomotor. El objetivo del proyecto es dilucidar la posible función protectora de la autofagia mediada por la Ocn de las MN para mantenerla actividad locomotora. Al lograrlo, el equipo de CAJAL podría descubrir nuevos tratamientos para el deterioro del sistema locomotor senil.

Objetivo

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.