what is in-BDNF?

ultima modifica 26/11/2013 17:04

The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is known to exert multiple effects on the central nervous system: not only it increases survival of adult neurons and favors neuronal differentiation of neural progenitor cells, but is also implicated in plastic changes at structural (for example, dendritogenesis) and synaptic level (for example, potentiation of excitatory synapses). Because of these effects, modulation of the BDNF system has been proposed as a novel therapeutic approach for many neurological diseases. This goal, however, turned out to be difficult to reach, for at least two orders of still unresolved problems.

First, BDNF may exert different, and sometimes even opposite effects, depending on a number of factors: alternative splicing of its mRNA, processing of the pro- into the mature form, specific cellular domain of action, receptor subtype (high- or low-affinity), signaling pathway activated. Understanding in detail the biology of BDNF and finding ways to interfere selectively with specific aspects of it will be essential to develop effective therapeutic strategies that are not compromised by unwanted (or evenparadoxical) side effects. Second, BDNF is a peptide in nature and it should be targeted specifically to the brain area affected by a disease to avoid undesired sideeffects. This consideration poses the question of delivery: strategies should be developed to deliver the BDNF-acting therapy selectively at the site where it is needed.

Aim of this project is to contribute to the solution of these problems, identifying new therapeutic strategies and applying them to major neurological diseases. This collaborative proposal brings together 8 research groups, very active in the fields of neurotrophins and of synaptic transmission, with a special interest and focus on the molecular and cellular mechanisms of neurological disorders, and with a well-proven and consolidated track record of effective collaboration. Partners will exchange reagents, experimental protocols and know-how, cell lines and transgenic mice models.

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Project coordinator: prof. Michele Simonato, michele.simonato@unife.it