Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Clinically, it is characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroinflammation can play a role in PD pathophysiology, being associated with its onset and progression. Nevertheless, several key points concerning the neuroinflammatory process in PD remain to be answered. Bearing this in mind, in the present review, we cover the impact of neuroinflammation on PD by exploring the role of inflammatory cells (i.e., microglia and astrocytes) and the interconnections between the brain and the peripheral system. Furthermore, we discuss both the innate and adaptive immune responses regarding PD pathology and explore the gut–brain axis communication and its influence on the progression of the disease.

BackgroundKRAS is an EGFR effector in the RAS/RAF/ERK cascade that is mutated in about 40% of metastatic colorectal cancer (mCRC). Activating mutations in codons 12 and 13 of the KRAS gene are the only established negative predictors of response to anti-EGFR therapy and patients whose tumors harbor such mutations are not candidates for therapy. However, 40 to 60% of wild-type cases do not respond to anti-EGFR therapy, suggesting the involvement of other genes that act downstream of EGFR in the RAS-RAF-MAPK and PI3K-AKT pathways or activating KRAS mutations at other locations of the gene.MethodsDNA was obtained from a consecutive series of 201 mCRC cases (FFPE tissue), wild-type for KRAS exon 2 (codons 12 and 13). Mutational analysis of KRAS (exons 3 and 4), BRAF (exons 11 and 15), and PIK3CA (exons 9 and 20) was performed by high resolution melting (HRM) and positive cases were then sequenced.ResultsOne mutation was present in 23.4% (47/201) of the cases and 3.0% additional cases (6/201) had two concomitant mutations. A total of 53 cases showed 59 mutations, with the following distribution: 44.1% (26/59) in KRAS (13 in exon 3 and 13 in exon 4), 18.6% (11/59) in BRAF (two in exon 11 and nine in exon 15) and 37.3% (22/59) in PIK3CA (16 in exon 9 and six in exon 20). In total, 26.4% (53/201) of the cases had at least one mutation and the remaining 73.6% (148/201) were wild-type for all regions studied. Five of the mutations we report, four in KRAS and one in BRAF, have not previously been described in CRC. BRAF and PIK3CA mutations were more frequent in the colon than in the sigmoid or rectum: 20.8% vs. 1.6% vs. 0.0% (P=0.000) for BRAF and 23.4% vs. 12.1% vs. 5.4% (P=0.011) for PIK3CA mutations.ConclusionsAbout one fourth of mCRC cases wild-type for KRAS codons 12 and 13 present other mutations either in KRAS, BRAF, or PIK3CA, many of which may explain the lack of response to anti-EGFR therapy observed in a significant proportion of these patients.

The crosstalk between glial cells and neurons represents an exceptional feature for maintaining the normal function of the central nervous system (CNS). Increasing evidence has revealed the importance of glial progenitor cells in adult neurogenesis, reestablishment of cellular pools, neuroregeneration, and axonal (re)myelination. Several types of glial progenitors have been described, as well as their potentialities for recovering the CNS from certain traumas or pathologies. Among these precursors, glial‐restricted precursor cells (GRPs) are considered the earliest glial progenitors and exhibit tripotency for both Type I/II astrocytes and oligodendrocytes. GRPs have been derived from embryos and embryonic stem cells in animal models and have maintained their capacity for self‐renewal. Despite the relatively limited knowledge regarding the isolation, characterization, and function of these progenitors, GRPs are promising candidates for transplantation therapy and reestablishment/repair of CNS functions in neurodegenerative and neuropsychiatric disorders, as well as in traumatic injuries. Herein, we review the definition, isolation, characterization and potentialities of GRPs as cell‐based therapies in different neurological conditions. We briefly discuss the implications of using GRPs in CNS regenerative medicine and their possible application in a clinical setting.Main PointsGRPs are progenitors present in the CNS with differentiation potential restricted to the glial lineage. These cells have been employed in the treatment of a myriad of neurodegenerative and traumatic pathologies, accompanied by promising results, herein reviewed.

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