Enrico TONGIORGI
Head of the Cellular and Developmental Neurobiology Lab
Department of Life Sciences
University of Trieste
Via E. Weiss 2 - Pal. Q
34128 Trieste
ITALY
Website Enrico Tongiorgi
Programm
”Regulation and dysregulation of the “spatial & quantitative code” of BDNF mRNA transcripts”
Brain-Derived Neurotrophic Factor (BDNF) is a key regulator of neuronal development and plasticity and has recently emerged as new pharmaceutical target in most neuropsychiatric diseases. However, BDNF gene has a complex regulation. The same protein is produced from 22 different transcripts in rodents (34 in humans), obtained by alternative splicing. Some years ago, we proposed that the different BDNF mRNA variants provide a “spatial and quantitative code” for BDNF protein production in different subcellular domains and at different levels depending on the nature of the receptors activated. Indeed, the different BDNF transcripts have a differential subcellular localization in neurons, being segregated between soma, proximal or distal dendrites and support local translation of BDNF protein with spatially restricted effects on dendrites development and synaptic plasticity. More recently, we explored the impact of the dysregulation of such a code in diseases characterized by neurons with atrophic dendrites. In particular, we focused on Rett Syndrome (RTT), a neurodevelopmental disorder caused by the mutation of MeCP2 (Methyl CpG binding protein 2) leading to mental retardation and seizures. We investigated the association of BDNF mRNA with the three major classes of RNA granules, transporting granules (TG), stress granules (SG) or processing bodies (PB). We propose dysregulation of dendritic BDNF mRNA trafficking as new molecular mechanisms underlying neuronal atrophy in RTT.
Host: Isabella SALZER
Contact for questions: Helmut KUBISTA