New Insights into Intracellular Pathways and Therapeutic Targets in CNS Diseases

The intracellular signalling network machinery, responding to different micro-environmental cues, regulates all aspects of cellular physiology, including metabolism, gene expression and modification, proliferation, differentiation and programmed cell death. Indeed, changes in the expression of cell surface receptors and/or their mutations, as well as ligand abundance, can have profound effects on cell physiology of the central nervous system and disarray of cell signalling often lies beneath the cause of neuronal diseases. New interesting knowledge has been recently gathered demonstrating the importance of canonical developmental pathways such as Sonic Hedgehog (SHH), Wnt/b-catenin and Notch-3 in neuronal homeostasis. As well, the role of autophagosomes generating pathways has recently been involved in conditions such as neuroinflammation, Alzheimer's and Parkinson’s diseases, brain tumours, and damages due to cerebral ischemia and reperfusion, with a specific attention on the accumulation of ROS-generating damaged mitochondria.

Similarly, recent investigations also highlighted the relevance of signalling cascade regulation on pharmaco-resistance to treatment with DNA Damage Repair inhibitors in tumours of the CNS. Interestingly, the identification of the role of new and established cell signalling markers may lead to a complete change in the clinical classification of several CNS pathologies, with profound implications for prognosis and therapy.

In this scenario, this Research Topic aims to provide new insights on the actors of cell signalling in the CNS and how their expression and activity couples and dialogues with the epi-genome, ultimately affecting the occurrence and maintenance of several neuronal disorders. We are therefore scouting for groundbreaking studies on new intracellular markers and innovative medical, pharmacological and bio-molecular strategies to deploy for interfering with pathogenic signalling cascades in the CNS.

A Special Note: We would like to dedicate this special issue to the memory of Prof. Matteo Caleo, an exceptional mentor and a friendly colleague. We will always remember his integrity, his kindness, his humility and his smile. We will try to put his lessons into practice, in our research and everyday life.