In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population. These cells function to maintain homeostasis and are directly involved in the development and resolution of neuroinflammatory processes. Also, following inflammation, circulating monocytes can be recruited and enter the CNS, therefore contributing to brain pathology. These cell populations have now been identified as key players in CNS pathology, including autoimmune diseases, such as multiple sclerosis, and degenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. Here, we review the evidence on the involvement of CNS macrophages in neuroinflammation and the advantages, pitfalls, and translational opportunities of pharmacological interventions targeting these heterogeneous cellular populations for the treatment of brain diseases.

The extracellular matrix (ECM) plays an important role in the regulation of the tissue microenvironment and in the maintenance of cellular homeostasis. Several proteins with a proteolytic activity toward several ECM components are involved in the regulation and remodeling of the ECM. Among these, Matrix Metalloproteinases (MMPs) are a class of peptidase able to remodel the ECM by favoring the tumor invasive processes. Of these peptidases, MMP-9 is the most involved in the development of cancer, including that of melanoma. Dysregulations of the MAPKs and PI3K/Akt signaling pathways can lead to an aberrant overexpression of MMP-9. Even ncRNAs are implicated in the aberrant production of MMP-9 protein, as well as other proteins responsible for the activation or inhibition of MMP-9, such as Osteopontin and Tissue Inhibitors of Metalloproteinases. Currently, there are different therapeutic approaches for melanoma, including targeted therapies and immunotherapies. However, no biomarkers are available for the prediction of the therapeutic response. In this context, several studies have tried to understand the diagnostic, prognostic and therapeutic potential of MMP-9 in melanoma patients by performing clinical trials with synthetic MMPs inhibitors. Therefore, MMP-9 may be considered a promising molecule for the management of melanoma patients due to its role as a biomarker and therapeutic target.

Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis

Pathogenic role for macrophage migration inhibitory factor in glioblastoma and its targeting with specific inhibitors as novel tailored therapeutic approach Pathogenic role for macrophage migration inhibitory factor in glioblastoma and its targeting with specific inhibitors as novel tailored therapeutic approach

There is recent evidence to indicate the existence of an inverse association between the incidence of neurological disorders and cancer development. Concurrently, the transcriptional pathways responsible for the onset of glioblastoma multiforme (GBM) and Alzheimer's disease (AD) have been found to be mutually exclusive between the two pathologies. Despite advancements being made concerning the knowledge of the molecular mechanisms responsible for the development of GBM and AD, little is known about the identity of the microRNA (miRNAs or miRs) involved in the development and progression of these two pathologies and their possible inverse expression patterns. On these bases, the aim of the present study was to identify a set of miRNAs significantly de‑regulated in both GBM and AD, and hence to determine whether the identified miRNAs exhibit an inverse association within the two pathologies. For this purpose, miRNA expression profiling datasets derived from the Gene Expression Omnibus (GEO) DataSets and relative to GBM and AD were used. Once the miRNAs significantly de‑regulated in both pathologies were identified, DIANA‑mirPath pathway prediction and STRING Gene Ontology enrichment analyses were performed to establish their functional roles in each of the pathologies. The results allowed the identification of a set of miRNAs found de‑regulated in both GBM and AD, whose expression levels were inversely associated in the two pathologies. In particular, a strong negative association was observed between the expression levels of miRNAs in GBM compared to AD, suggesting that although the molecular pathways behind the development of these two pathologies are the same, they appear to be inversely regulated by miRNAs. Despite the identification of this set of miRNAs which may be used for diagnostic, prognostic and therapeutic purposes, further functional in vitro and in vivo evaluations are warranted in order to validate the diagnostic and therapeutic potential of the identified miRNAs, as well as their involvement in the development of GBM and AD.