A group of researchers from the Cnr Institutes for Biomedical Research and Innovation (Irib) and Biochemistry and Cell Biology (Ibbc), along with colleagues from the European Institute for Brain Research (Ebri) and the University of Catania, have deciphered the ‘program’, this is the set of instructions that regulate Neuronal turnover. The results have been published in the journal Cells .
Neuronal turnover is essential to the development, maintenance, and renewal of our nervous system. It is finely regulated by opposing stimuli, which can support neuronal survival or induce apoptosis, a genetically programmed cell suicide. Dysfunction in the molecular mechanisms involved in neuronal turnover is the basis of pathological conditions and can cause developmental defects, tumors, or neurodegenerative diseases.
“For some time, we have been on the trail of the mechanisms that govern the life and death of neurons,” says Sebastiano Cavallaro, Director of Research at the Institute for Biomedical Research and Innovation (Cnr-Irib), head of the Genome Laboratory in Catania. Coordinator of research published in the journal cellsWe have for the first time deciphered the set of instructions that control these very important processes and the effects that their disruptions can have on human disease. Just as in computers, where failures often stem from faulty software, altered neuronal turnover can result from a malfunctioning program. “.
The analysis of transcription, that is, the set of messenger RNAs, was first allowed to characterize the transcriptional programme, that is, the genes involved in the stages in which a neuron decides to perform apoptosis or not. This program appears to be common to other cells, being involved not only in neurological diseases but also in psychiatric and oncological diseases. Moreover, drugs already used to treat these diseases are able to restore this transcription program, highlighting its clinical implications.
In order to decode the program, this is the set of instructions, which regulate neuronal turnover, a reverse-engineered process was used to identify the transcription factors that, with hierarchical organization, direct the transcription program. The regulation of these transcription factors by existing pharmacological compounds could provide new therapeutic insights. Cavallaro concludes, “Deciphering the code of cellular life or death can help identify failure and treatment in many diseases through innovative pharmacology that is not only focused on the end goals, but directed at the programs that control them.”
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