PROJECT: JTC2009: NANOSYN

Neural communication depends on permanent exo- and endocytic vesicle cycling at the synapse, sustained by a complex molecular machinery. Cysteine String Protein-alpha (CSP-alpha) is a synaptic vesicle protein proposed to protect nerve terminals from molecular stress associated with the continuous synaptic activity. Knock-out mice lacking CSP-alpha, suffer from early synaptic degeneration by poorly understood mechanisms. Molecular manipulation of synapses with genetic vectors is feasible but restricted to certain type of synapses and time-limited by gene expression. We will set-up a novel approach based on highly functionalized nanoparticles for fast delivery of proteins into neurons and glia under temporal and spatial control. Our goal is to investigate molecular mechanisms of synaptic degeneration and to get insight into protein delivery in neurons. We will investigate if CSP-alpha inactivation in astrocytes alters the release of gliotransmiters and if it contributes to synaptic degeneration. We bring together a multidisciplinary consortium with experience in molecular physiology of the synapse, design and synthesis of nanoparticles and analysis of cell function with advanced microscopy techniques. We expect to contribute to understand general mechanisms of synaptic maintenance that prevent neurodegeneration. In addition, we expect to open new possibilities to study and to interfere with molecular mechanisms of neurodegeneration in specific models of human diseases using nanoparticles-mediated protein delivery.