Parallel and massive sequencing of total RNA samples derived from different samples are possible thanks to the use of NGS (Next Generation Sequencing) technologies. This allowed characterizing the transcriptomic profile of both cell and tissue populations, increasing the knowledge of the molecular pathological processes of complex diseases, such as neurodegenerative diseases (NDs). Among the NDs, Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive loss of motor neurons (MNs), and, to date, the diagnosis is often made by exclusion because there is no specific symptomatologic picture. For this reason, it is important to search for biomarkers that are clinically useful for carrying out a fast and accurate diagnosis of ALS. Thanks to various studies, it has been possible to propose several molecular mechanisms associated with the disease, some of which include the action of non-coding RNA, including circRNAs, miRNAs, and lncRNAs which will be discussed in the present review. The evidence analyzed in this review highlights the importance of conducting studies to better characterize the different ncRNAs in the disease to use them as possible diagnostic, prognostic, and/or predictive biomarkers of ALS and other NDs.

Age-related macular degeneration (AMD) showed several processes and risk factors in common with neurodegenerative disorders (NDDs). The present work explored the existence of genetic determinants associated with AMD, which may provide insightful clues concerning its relationship with NDDs and their possible application into the clinical practice. In this study, 400 AMD patients were subjected to the genotyping analysis of 120 genetic variants by OpenArray technology. As the reference group, 503 samples representative of the European general population were utilized. Statistical analysis revealed the association of 23 single-nucleotide polymorphisms (SNPs) with AMD risk. The analysis of epistatic effects revealed that ARMS2, IL6, APOE, and IL2RA could contribute to AMD and neurodegenerative processes by synergistic modulation of the expression of disease-relevant genes. In addition, the bioinformatic analysis of the associated miRNA variants highlighted miR-196a, miR-6796, miR-6499, miR-6810, miR-499, and miR-7854 as potential candidates for counteracting AMD and neurodegenerative processes. Finally, this work highlighted the existence of shared disease mechanisms (oxidative stress, immune-inflammatory response, mitochondrial dysfunction, axonal guidance pathway, and synaptogenesis) between AMD and NDDs and described the associated SNPs as candidate biomarkers for developing novel strategies for early diagnosis, monitoring, and treatment of such disorders in a progressive aging population.

Background Plasma lipid profile and anthropometric variables are known to be under strong genetic control and the identification of genetic variants associated with bioclinical parameters is of considerable public health importance. In this study, a young cohort of healthy individuals was genotyped for genes related to health and pathological conditions, to analyze the association of single nucleotide polymorphisms (SNPs) with different bioclinical parameters, adherence to the Mediterranean Diet (MD) and physical activity, studying the role of lifestyle and body composition parameters on biochemical metabolic profile. Methods Association analysis of single variants in the genes of lipoprotein lipase (LPL), fibronectin type III domain containing protein 5 (FNDC5), and peroxisome proliferator-activated receptor-gamma (PPARγ) and haplotype analyses were performed. Results Multiple (n = 14) common variants in the three genes demonstrated a significant effect on plasma lipoprotein-lipid levels and/or on biochemical parameters in our sample. Specifically, SNPs were related to lipid metabolism (rs3866471, rs4922115, rs11570892, rs248, rs316, rs1059507, rs1801282) or glycemic profile (rs3208305) or anthropometric parameters (rs3480, rs726344, rs1570569) for a total of 26 significant associations (P < 0.01 and/or P < 0.05) and two haplotypes, for the first time, were strongly associated with lipid and body composition parameters. Interestingly, we identified twenty-four new variants not previously described in the literature and a novel significant association between rs80143795 and body composition. Conclusions In this study we confirm the association between these SNPs on lipid metabolism and body parameters also in a young cohort, indicating the important role of these genetic factors as determinants of health.

Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease whose causes are unclear. The first ALS gene associated with the autosomal dominant form of the disease was SOD1. This gene has a high rate of rare variants, and an appropriate classification is essential for a correct ALS diagnosis. In this study, we re-evaluated the classification of all previously reported SOD1 variants (n = 202) from ALSoD, project MinE, and in-house databases by applying the ACMG-AMP criteria to ALS. New bioinformatics analysis, frequency rating, and a thorough search for functional studies were performed. We also proposed adjusting criteria strength describing how to apply them to SOD1 variants. Most of the previously reported variants have been reclassified as likely pathogenic and pathogenic based on the modified weight of the PS3 criterion, highlighting how in vivo or in vitro functional studies are determining their interpretation and classification. Furthermore, this study reveals the concordance and discordance of annotations between open databases, indicating the need for expert review to adapt the study of variants to a specific disease. Indeed, in complex diseases, such as ALS, the oligogenic inheritance, the presence of genes that act as risk factors and the reduced penetration must be considered. Overall, the diagnosis of ALS remains clinical, and improving variant classification could support genetic data as diagnostic criteria.

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