Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of α-Synuclein aggregates and the degeneration of dopaminergic neurons in substantia nigra in the midbrain. Although the exact mechanisms of neuronal degeneration in PD remain largely elusive, various pathogenic factors, such as α-Synuclein cytotoxicity, mitochondrial dysfunction, oxidative stress, and pro-inflammatory factors, may significantly impair normal neuronal function and promote apoptosis. In this context, neuroinflammation and autophagy have emerged as crucial processes in PD that contribute to neuronal loss and disease development. They are regulated in a complex interconnected manner involving most of the known PD-associated genes. This review summarizes evidence of the implication of neuroinflammation and autophagy in PD and delineates the role of inflammatory factors and autophagy-related proteins in this complex condition. It also illustrates the particular significance of plasma and serum immune markers in PD and their potential to provide a personalized approach to diagnosis and treatment.

MicroRNAs (miRNAs) are short non-coding RNA molecules with a well-recognized role in gene expression mostly at the post-transcriptional level. Recently, dysregulation of miRNAs and miRNA-mRNA interactions has been associated with CNS diseases, including numerous psychiatric disorders. Dynamic changes in the expression profiles of circulating miRNA are nowadays regarded as promising non-invasive biomarkers that may facilitate the accurate and timely diagnosis of complex conditions. In this study, we investigated the gene expression patterns of four miRNAs, which were previously reported to be dysregulated in pooled serum samples taken from Autism Spectrum Disorder (ASD) patients and typically developing children. The performance of a diagnostic model for ASD based on these four miRNAs was assessed by a receiver operating characteristic (ROC) curve analysis, which evaluates the diagnostic accuracy of the investigated miRNA biomarkers for ASD. Finally, to examine the potential modulation of CNS-related biological pathways, we carried out target identification and pathway analyses of the selected miRNAs. Significant differential expression for all the four studied miRNAs: miR-500a-5p, miR-197-5p, miR-424-5p, and miR-664a-3p, was consistently measured in the samples from ASD patients. The ROC curve analysis demonstrated high sensitivity and specificity for miR-500a-5p, miR-197-5p, and miR-424-5p. With all miRNA expression data integrated into an additive ROC curve, the combination of miR-500a-5p and miR-197-5p provided the most powerful diagnostic model. On the other hand, the mRNA target mining showed that miR-424-5p and miR-500-5p regulate pools of target mRNA molecules which are enriched in a number of biological pathways associated with the development and differentiation of the nervous system. The steady expression patterns of miR-500a-5p, miR-197-5p, miR-424-5p, and miR-664a-3p in ASD children suggest that these miRNAs can be considered good candidates for non-invasive molecular biomarkers in the study of ASD patients. The highest diagnostic potential is manifested by miR-500a-5p and miR-197-5p, whose combined ROC curve demonstrates very strong predictive accuracy.

Background: NGF is a molecule with a pleiotropic role, affecting neuro-immune functions, energy homeostasis, and synaptic plasticity. The mechanisms of NGF-induced neuronal differentiation are well established, but its effect on mitochondria in autism spectrum disorder (ASD) is still unclear. We hypothesize that NGF-induced neuronal development requires large amounts of energy, and mitochondria in ASD are overloaded to meet the new functional requirements. Method: The study includes primary diagnosed ASD children. Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from both patients and typically developing children (TDC). PBMCs were analyzed with Seahorse XFp, and plasma NGF protein levels were measured. Results: We detected nearly 50% higher NGF levels and approximately 40% elevation in spare respiratory capacity in ASD compared to TDC. These findings are consistent with the observed difference in maximal respiration, which was also significantly higher in the patient group. Both mitochondrial respiration and NGF plasma levels exhibit a strong potential to discriminate children with ASD from TDC. Conclusions: This study is the first to link elevated NGF with mitochondrial respiration and altered energy homeostasis in ASD. High NGF correlates with basic bioenergetic signatures that may be used as a screening tool to improve early diagnosis and clinical follow-up in ASD.

Cytokines are a diverse group of signaling proteins that regulate immune responses by mediating cell communication. Among them, interleukins (ILs) play essential roles in immune regulation, influencing diverse cell processes through tightly controlled signaling networks. Dysregulation of interleukin signaling could lead to chronic inflammation, contributing to the development of autoimmune and inflammatory diseases as well as cancer. IL-26, a cytokine of the IL-10 family, has emerged as a unique modulator of immune function. Although structurally related to IL-10 and sharing one of its receptor subunits, IL-26 exerts distinct biological effects, particularly in promoting inflammatory responses and interacting with extracellular DNA to activate immune pathways. Increasing evidence implicates IL-26 in the development of several chronic conditions, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, asthma, and various types of cancer. This review summarizes current knowledge on IL-26’s biology, including its structural and receptor characteristics, immunomodulatory functions, and roles in inflammation and disease. Understanding IL-26’s dual functions in normal and inflammatory states may provide insights into novel therapeutic strategies targeting IL-26-mediated pathways in pathological conditions.