Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in several areas of the central nervous system (CNS). Substantial evidence has documented a common inflammatory mechanism in neurodegeneration. It is known that classical anti-inflammatory agents, steroids and nonsteroidal anti-inflammatory drugs, have not played a major role in the management of CNS inflammatory conditions. This may be partly due to the natural compartmentation of the brain by the blood-brain barrier. Thus, there is much interest in developing novel anti-inflammatory drugs that may help to prevent or ameliorate CNS inflammation. Resveratrol (RSV) has received considerable attention over the last several decades. Experimental studies have revealed its benefits in several human disease models, including cardio- and neuro-protection, immune regulation and cancer chemoprevention. The broad action spectrum of RSV is explained by the involvement of numerous signaling networks and cellular effector mechanisms. Among them, apoptotic and antioxidant targets have been implicated. Recently, also anti-neuroinflammatory activity has been observed. A number of studies demonstrated that RSV mediates the downregulation of various inflammatory biomarkers such as tumor necrosis factor, cyclooxygenase 2, inducible nitric oxide synthase and interleukins. This activity seems to depend on some structural features of RSV such as the number and the position of hydroxyl groups. In this review, a comprehensive account of multiple intracellular RSV targets involved in neuroinflammation and its analogues design will be treated, pointing to structure/activity relationships.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression signatures of brain cortex of ASD patients, by using two publicly available RNA-seq studies, in order to discover new ASD-related genes. Results: We detected 1567 differentially expressed genes (DEGs) by meta-analysis, where 1194 were upregulated and 373 were downregulated genes. Several ASD-related genes previously reported were also identified. Our meta-analysis identified 235 new DEGs that were not detected using the individual RNA-seq studies used. Some of those genes, including seven DEGs (PAK1, DNAH17, DOCK8, DAPP1, PCDHAC2, and ERBIN, SLC7A7), have been confirmed in previous reports to be associated with ASD. Gene Ontology (GO) and pathways analysis showed several molecular pathways enriched by the DEGs, namely, osteoclast differentiation, TNF signaling pathway, complement and coagulation cascade. Topological analysis of protein–protein interaction of the ASD brain cortex revealed proteomics hub gene signatures: MYC, TP53, HDAC1, CDK2, BAG3, CDKN1A, GABARAPL1, EZH2, VIM, and TRAF1. We also identified the transcriptional factors (TFs) regulating DEGs, namely, FOXC1, GATA2, YY1, FOXL1, USF2, NFIC, NFKB1, E2F1, TFAP2A, HINFP. Conclusion: Novel core genes and molecular signatures involved with ASD were identified by our meta-analysis.