title: Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets.
abstract: A change in the delicate equilibrium between apoptosis and survival regulates the neurons fate during the development of nervous system and its homeostasis in adulthood. Signaling pathways promoting or protecting from apoptosis are activated by multiple signals, including those elicited by neurotrophic factors, and depend upon specific transcriptional programs. To decipher the rescue program induced by substance P (SP) in cerebellar granule neurons, we analyzed their whole-genome expression profiles after induction of apoptosis and treatment with SP. Transcriptional pathways associated with the survival effect of SP included genes encoding for proteins that may act as pharmacological targets. Inhibition of one of these, the Myc pro-oncogene by treatment with 10058-F4, reverted in a dose-dependent manner the rescue effect of SP. In addition to elucidate the transcriptional mechanisms at the intersection of neuronal apoptosis and survival, our systems biology-based perspective paves the way towards an innovative pharmacology based on targets downstream of neurotrophic factor receptors.
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council , Via Paolo Gaifami, 18, Catania 95125, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Paparone
authors.affiliation: Institute of Cell Biology and Neurobiology, Italian National Research Council, Via del Fosso di Fiorano 64, Roma 00143, Italy; European Brain Research Institute, Via del Fosso di Fiorano 64, Roma 00143, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Severini
authors.affiliation: Institute of Cell Biology and Neurobiology, Italian National Research Council , Via del Fosso di Fiorano 64, Roma 00143, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Ciotti
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania , Catania 95125, Italy.
authors.forename: V
authors.initials: V
authors.lastname: D'Agata
authors.affiliation: European Brain Research Institute , Via del Fosso di Fiorano 64, Roma 00143, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calissano
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council , Via Paolo Gaifami, 18, Catania 95125, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cavallaro