faceted 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.

Drug target identification at the crossroad of neuronal apoptosis and survival

Simona Paparone;Cinzia Severini;Maria Teresa Ciotti;Pietro Calissano;Sebastiano Cavallaro
2017

Abstract

faceted 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.
2017
Istituto di Scienze Neurologiche - ISN - Sede Mangone
Istituto di Biologia Cellulare e Neurobiologia - IBCN - Sede Monterotondo Scalo
Istituto di Biochimica e Biologia Cellulare - IBBC
Apoptosis
cerebellar granule neurons
drug target
insulin-like growth factor-1
pituitary adenylyl cyclase-activating polypeptide
systems biology
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/357641
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