title: Drug target identification at the crossroad of neuronal apoptosis and survival.
abstract: Inappropriate activation of apoptosis may contribute to neurodegeneration, a multifaceted process that results in various chronic disorders, including Alzheimer's and Parkinson's diseases. Several in vitro and in vivo studies demonstrated that neuronal apoptosis is a multi-pathway cell-death program that requires RNA synthesis. Thus, transcriptionally activated genes whose products induce cell death can be triggered by different stimuli and antagonized by neurotrophic factors. Systems biology is now unveiling the series of intracellular signaling pathways and key drug targets at the intersection of neuronal apoptosis and survival. Areas covered: This review introduces a genomic approach that can be used to elucidate the systems biology of neuronal apoptosis and survival, and to rationally select drug targets, no longer oriented to emulate the action of growth factors at the membrane receptor level, but rather to modulate their downstream signals. Expert opinion: The advent of genomics is offering an unprecedented opportunity to explore how the delicate balance between apoptosis and survival-inducing signals triggers a transcriptional program. Characterization of this program can be useful to identify potential pharmacological targets for existing drugs. Such knowledge might pave the way towards an innovative pharmacology.
authors.affiliation: a Institute of Neurological Sciences , Italian National Research Council , Catania , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Maino
authors.affiliation: a Institute of Neurological Sciences , Italian National Research Council , Catania , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Paparone
authors.affiliation: b Institute of Cell Biology and Neurobiology , Italian National Research Council , Roma , Italy.|c European Brain Research Institute , 00143 Roma , Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Severini
authors.affiliation: b Institute of Cell Biology and Neurobiology , Italian National Research Council , Roma , Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.affiliation: d Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology , University of Catania , 95125 Catania , Italy.
authors.forename: Velia
authors.initials: V
authors.lastname: D'agata
authors.affiliation: c European Brain Research Institute , 00143 Roma , Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Calissano
authors.affiliation: a Institute of Neurological Sciences , Italian National Research Council , Catania , Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015195:Drug Design; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D015398:Signal Transduction; D049490:Systems Biology
keywords: Apoptosis; cerebellar granule neurons; drug target; insulin-like growth factor-1; pituitary adenylyl cyclase-activating polypeptide; systems biology