Gliomas are considered the most common primary brain tumors in adults, and over half of all brain tumors are gliomas [1,2,3,4]. Glioblastoma multiforme (GBM) is regarded as one of the most aggressive and lethal types of gliomas [5,6,7,8]. Unfortunately, the cause of the disease is unknown in most GBM patients [9]. The current standard of care treatment includes surgical resection followed by radiotherapy and chemotherapy. Even after treatment, patients with GBM typically have a median survival of approximately 14 months [10,11,12]. In recent studies, glioblastoma has been classified into three subtypes based on transcriptome analysis of the GBM tumors: proneural, classical, and mesenchymal [13,14]. The mesenchymal subtype of GBM is associated with the worst prognosis due to its expression of neural stem cell markers and the creation of an inflammatory microenvironment with increased angiogenesis [15]. Recognizing and utilizing these molecular subtypes in GBM therapy could facilitate personalized treatment and improve patient outcomes. Research has shown that glioma cells exhibit a greater responsiveness to treatment through autophagy as opposed to apoptosis [16], making the autophagy pathway a compelling target in the GBM treatments. Also, according to a recent whole transcriptome expression data analysis, high expression levels of autophagy-related genes are detected in classical and mesenchymal subtypes, the more malignant tumor subtypes [17,18].

Autophagy is a natural cellular process that plays a crucial role in maintaining cellular homeostasis, adapting to stress conditions, and promoting cell survival [19,20]. There are three different primary types of autophagy, which include microautophagy, chaperone-mediated autophagy, and macroautophagy [21]. These pathways are differentiated by the method by which cytosolic cargoes are delivered to the lysosome [22]. Microautophagy involves the lysosome utilizing direct membrane protrusion to take up cytoplasmic material for degradation [23]. Microautophagy has gained significant attention in recent research endeavors. It not only relates to macroautophagy regulation [21] but also plays a role in cancer and neurodegenerative disorders [24,25,26,27]. Chaperone-mediated autophagy (CMA) is a selective form of autophagy that targets specific individual proteins for degradation [28,29]. CMA involves cytosolic proteins with KFERQ-like motifs that are recognized by chaperone HSC70, and these proteins are delivered to the lysosomal-associated membrane protein 2A (LAMP2A), which allows for the translocation of these proteins into the lysosome for degradation [30]. Quite a few proteins involved in neurodegenerative disorders, including α-synuclein [31,32,33] and β-amyloid precursor protein [32], contain this motif. Thus, inhibiting CMA in neurons impairs neuronal function and leads to the accumulation of harmful proteins, thereby raising susceptibility to Alzheimer’s disease [34]. Macroautophagy (autophagy) plays a key role in cell physiology. Some of these roles include the degradation and recycling of damaged organelles, as well as the maintenance of normal cellular homeostasis [35]. The basic mechanism of autophagy has been well documented and involves the formation of a cytosolic double-membrane vesicle known as the autophagosome, which fuses with lysosomes to degrade its contents [36]. Macroautophagy generally occurs at low levels and can be further induced under specific stress conditions. Macroautophagy deteriorates cytoplasmic material into metabolites that can be used in biosynthetic processes or energy production for cell survival [37]. While autophagy primarily functions as a cytoprotective mechanism for degrading damaged organelles, uncontrolled autophagy can lead to detrimental consequences for the cell.