**6. Conclusions**

In this review, we discussed the role of BDNF in neurogenesis, differentiation, survival, synaptic plasticity, and transmission to reorganize the brain microenvironment. All BDNF gene products, such as proBDNF, mature BDNF, and even the isolated proBDNF domain, are known to exert functional activity. One of the most important features of BDNF is that it can act as a local, paracrine and/or autocrine factor, on both pre-synaptic and post-synaptic target sites. Here, we presented the contribution of altered BDNF signaling in the pathophysiology of brain diseases, including mental disorders (i.e., depression), neurodegenerative diseases, (i.e., Alzheimer's disease), and brain tumor (i.e., glioblastoma). BDNF is one of the best-studied synaptic molecules that efficiently modify synaptic strength and it can act as a mediator, modulator, or instructor of synaptic plasticity. In neurons, the cellular processes that regulate the amount of both BDNF mRNA and protein, the changes in the efficiency of secretion, and transport of BDNF protein may affect synaptic function and cell survival. BDNF is one of the most inspiring

molecules to better understand the disadvantageous synaptic learning underlying the etiology of depression, accompanied by the decline in the rate of adult neurogenesis and in spine densities. Furthermore, BDNF appears to exert a potent role in neuroprotection and/or brain regeneration by modulating signaling pathways such Ras-ERK-CREB, thus rendering neuronal cells resilient to neurodegeneration. Finally, BDNF appears to be crucial in the pathogenesis and development of brain tumors such as glioblastoma by reorganizing its microenvironment. Thus, understanding the physiologic and pathologic BDNF signaling and finding tools to modulate its expression (mRNA and/or protein) is a prerequisite for a potential BDNF-based therapy.

**Author Contributions:** Original draft preparation, writing and editing, L.C.-D., L.S.; original draft preparation, writing and review, F.V. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by program VALERE: VAnviteLli pEr la RicErca to L.C.D.

**Conflicts of Interest:** The authors declare no conflict of interest.
