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Lipids are hydrophobic molecules involved in a plethora of biological functions; for example, they are employed for the storage of energy, serve as essential constituents of cell membranes and participate in the assembly of bilayer configuration [...]

This Special Issue focused on the current understanding of signaling pathways as well as genetic and epigenetic features involved in the pathogenesis of brain tumors and other nervous system tumors, with emphasis on the development of novel therapeutic approaches aimed at improving the current standard of care [...]

Although initially regarded as a passive system to store energy, lipids are now considered to play crucial, structural and functional roles in almost all the biological processes involved in the regulation of physiological and pathological conditions [...]

International audience; The mevalonate (MVA)/cholesterol pathway is crucial for central nervous system (CNS) development and function and consequently, any dysfunction of this fundamental metabolic pathway is likely to provoke pathologic changes in the brain. Mutations in genes directly involved in MVA/cholesterol metabolism cause a range of diseases, many of which present neurologic and psychiatric symptoms. This raises the question whether other diseases presenting similar symptoms are related albeit indirectly to the MVA/cholesterol pathway. Here, we summarized the current literature suggesting links between MVA/cholesterol dysregulation and specific diseases, namely autism spectrum disorder and Rett syndrome.

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.

Gliomas are the most common and challenging malignancies of the central nervous system (CNS), due to their infiltrative nature, tendency to recurrence, and poor response to treatments. Indeed, despite the advances in neurosurgical techniques and in radiation therapy, the modest effects of therapy are still challenging. Moreover, tumor recurrence is associated with the onset of therapy resistance; it is therefore critical to identify effective and well-tolerated pharmacological approaches capable of inducing durable responses in the appropriate patient groups. Molecular alterations of the RTK/PI3K/Akt/mTOR signaling pathway are typical hallmarks of glioma, and several clinical trials targeting one or more players of this axis have been launched, showing disappointing results so far, due to the scarce BBB permeability of certain compounds or to the occurrence of resistance/tolerance mechanisms. However, as RTK/PI3K/mTOR is one of the pivotal pathways regulating cell growth and survival in cancer biology, targeting still remains a strong rationale for developing strategies against gliomas. Future rigorous clinical studies, aimed at addressing the tumor heterogeneity, the interaction with the microenvironment, as well as diverse posology adjustments, are needed—which might unravel the therapeutic efficacy and response prediction of an RTK/PI3K/mTOR-based approach.

The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the management of lipid disorders. Here, we investigated the role of bromodomain and extraterminal domain (BET) proteins in the regulation of lipid metabolism. To reach this aim, we used a loss-of-function approach by treating HepG2 cells with JQ1, a powerful and selective BET inhibitor. The main results demonstrated that BET inhibition by JQ1 efficiently decreases intracellular lipid content, determining a significant modulation of proteins involved in lipid biosynthesis, uptake and intracellular trafficking. Importantly, the capability of BET inhibition to slow down cell proliferation is dependent on the modulation of cholesterol metabolism. Taken together, these data highlight a novel epigenetic mechanism involved in the regulation of lipid homeostasis.