Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.

The development of new gene-editing technologies has fostered the need for efficient and safe vectors capable of encapsulating large nucleic acids. In this work we evaluate the synthesis of large-size plasmid-loaded PLGA nanoparticles by double emulsion (considering batch ultrasound and microfluidics-assisted methodologies) and magnetic stirring-based nanoprecipitation synthesis methods. For this purpose, we characterized the nanoparticles and compared the results between the different synthesis processes in terms of encapsulation efficiency, morphology, particle size, polydispersity, zeta potential and structural integrity of loaded pDNA. Our results demonstrate particular sensibility of large pDNA for shear and mechanical stress degradation during double emulsion, the nanoprecipitation method being the only one that preserved plasmid integrity. However, plasmid-loaded PLGA nanoparticles synthesized by nanoprecipitation did not show cell expression in vitro, possibly due to the slow release profile observed in our experimental conditions. Strong electrostatic interactions between the large plasmid and the cationic PLGA used for this synthesis may underlie this release kinetics. Overall, none of the methods evaluated satisfied all the requirements for an efficient non-viral vector when applied to large-size plasmid encapsulation. Further optimization or alternative synthesis methods are thus in current need to adapt PLGA nanoparticles as delivery vectors for gene editing therapeutic technologies.

Introduction: Despite the growing awareness of sexual dimorphism between males and females under pathological and physiological conditions, sex bias in biomedical research in animal models and patients is still present nowadays. The main objective of this work was to investigate sex differences in constitutive long non‐coding RNA expression in spinal cord and skeletal muscle from wild‐type mice.Materials and Methods: To assess the influence of gender on long non‐coding RNAs, we extracted RNA from tissues of male and female mice and analyzed the expression on nine long non‐coding RNAs, selected for being among the most commonly studied or exerting an important role in muscle, at 50, 60, and 120 days of age.Results and Discussion: We observed age‐ and tissue‐dependent significant sex differences, being more prominent in skeletal muscle. We also studied the effect of sex steroid hormones on long non‐coding RNA expression in vitro, noticing a modulation of long non‐coding RNA levels upon estradiol and dihydrotestosterone treatment in muscle.Conclusions: Taken together, results obtained evidenced sex differences on constitutive long non‐coding RNA expression and suggested an influence of steroid hormones complementary to other possible factors. These findings emphasize the importance of including both sexes in experimental design to minimize any potential sex bias.

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease. The expression profiles of 12 lncRNAs, selected from the literature, were evaluated across different disease stages in tissue and muscle biopsies from the SOD1 ^G93A transgenic mouse model of ALS. Nine out of the 12 lncRNAs were differentially expressed, with Pvt1, H19 and Neat1 showing notable increases in the symptomatic stages of the disease, and suggesting their potential as candidate biomarkers to support diagnosis and key players in muscle pathophysiology in ALS. Furthermore, the progression of Myhas and H19 RNA levels across disease stages correlated with longevity in the SOD1 ^G93A animal model, effectively discriminating between long- and short-term survival individuals, thereby highlighting their potential as prognostic indicators. These findings underscore the involvement of lncRNAs, especially H19 and Myhas, in ALS pathophysiology, offering novel insights for diagnostic, prognostic and therapeutic targets.

Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis.

Sarcopenia, the loss of muscle mass and function generally associated to age, leads to increased dependence and mortality in older adults. Despite its clinical significance, unclear molecular mechanisms hinder the development of universal diagnostic and therapeutic monitoring methods. Recent research suggests long non-coding RNAs (lncRNAs) as potential biomarkers for muscle damage and sarcopenia. This study investigates the role of six specific lncRNAs as biomarkers for diagnosing and monitoring sarcopenia following physical training. For this purpose, an initial cohort of participants was divided into two experiments: Trial 1, a cross-sectional study comprising 54 sarcopenic patients and 29 robust controls, both including men and women; Trial 2, a non-randomized controlled trial, where the same sarcopenic patients from Trial 1 were divided in two groups: a Control Group (CG, n = 15); and a Trained Group (TG, n = 22). RNA was extracted from serum samples for all the participants, and the expression of 6 lncRNA (PVT1, HOTAIR, MALAT1, NEAT1, GAS5, H19), selected from the literature, was quantified by RT-PCR and compared between the different groups. Statistical evaluation uncovered four lncRNAs with significantly distinct expression in Trial 1: PVT1 (LOG2FC = 1.194), GAS5 (LOG2FC = 0.8224), NEAT1 (LOG2FC = 1.497) and H19 (LOG2FC = −0.9958) and three lncRNA significantly different between TG and CG in Trial 2 (PVT1 (LOG2FC = −1.796), MALAT1 (LOG2FC = 2.834) and H19 (LOG2FC = 1.355). Among them, NEAT 1 stands aout as promissing diagnostic marker ans PVT1 and H19 may serve as both diagnosis and treatment monitoring, altough further validation in larger cohorts is needed to confirm these results.