Autophagic-Related Proteins in Brain Gliomas: Role, Mechanisms, and Targeting Agents

The aim of the present review is to discuss the autophagy, a well-known cellular process, able to remove damaged intracellular organelles as well as macromolecules and misfolded proteins. A dual role, as tumour promoter and tumour suppressor, has been attributed to autophagy. Therefore, we would analyse molecular mechanisms and regulatory pathways of autophagy, mainly concerning human astrocytic neoplasms. Moreover, information about relationships between autophagy, the tumour immune microenvironment, and glioma stem cells are furtherly illustrated. Drugs with higher selectivity for autophagy are actually developing and hopefully applied in the future to clinical practice. This modern perspective could help in the selection of patients with gliomas that are most likely to respond to the therapy of autophagy-inhibition. The present review focuses on the phenomenon of autophagy, a catabolic cellular process, which allows for the recycling of damaged organelles, macromolecules, and misfolded proteins. The different steps able to activate autophagy start with the formation of the autophagosome, mainly controlled by the action of several autophagy-related proteins. It is remarkable that autophagy may exert a double role as a tumour promoter and a tumour suppressor. Herein, we analyse the molecular mechanisms as well as the regulatory pathways of autophagy, mainly addressing their involvement in human astrocytic neoplasms. Moreover, the relationships between autophagy, the tumour immune microenvironment, and glioma stem cells are discussed. Finally, an excursus concerning autophagy-targeting agents is included in the present review in order to obtain additional information for the better treatment and management of therapy-resistant patients.