MicroRNAs (miRNAs) are a key gene regulator and play essential roles in several biological and pathological mechanisms in the human system. In recent years, plenty of miRNAs have been identified to be involved in the development of neurodegenerative disorders (NDDs), thus making them an attractive option for therapeutic approaches. Hence, in this review, we provide an overview of the current research of miRNA-based therapeutics for a selected set of NDDs, either for their high prevalence or lethality, such as Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, Friedreich’s Ataxia, Spinal Muscular Atrophy, and Frontotemporal Dementia. We also discuss the relevant delivery techniques, pertinent outcomes, their limitations, and their potential to become a new generation of human therapeutic drugs in the near future.

Superfruit guava (Psidium guajava L.) is one of the healthiest fruits due to its high antioxidant dietary fiber and vitamin content. However, the growth and development of this plant are severely affected by salinity stress, mostly at the seedling stage. MicroRNAs (miRNAs) are small, noncoding, endogenous, highly conserved RNA molecules that play key regulatory roles in plant development, organ morphogenesis, and stress response signaling. In this study, applying computational approaches and following high stringent filtering criteria, a total of 40 potential microRNAs belonging to 19 families were characterized from guava. The identified miRNA precursors formed stable stem-loop structures and exhibited high sequence conservation among diverse and evolutionarily distant plant species. Differential expression pattern of seven selected guava miRNAs (pgu-miR156f-5p, pgu-miR160c-5p, pgu-miR162-3p, pgu-miR164b-5p, pgu-miR166t, pgu-miR167a-5p, and pgu-miR390b-5p) were recorded under salinity stress and pgu-miR162-3p, pgu-miR164b-5p as well as pgu-miR166t were found to be the most affected ones. Using the psRNATarget tool, a total of 49 potential target transcripts of the characterized guava miRNAs were identified in this study which are mostly involved in metabolic pathways, cellular development, and stress response signaling. A biological network has also been constructed to understand the miRNA mediated gene regulation using the minimum free energy (MFE) values of the miRNA-target interaction. To the best of our knowledge, this is the first report of guava miRNAs and their targets.

Parkinson’s disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson’s Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe. We observed significant positive genetic correlations between PD and intracranial and subcortical brain volumes. Genome-wide association studies (GWAS) - pairwise analyses identified 210 genomic segments with shared aetiology between PD and at least one of these brain structures. Pathway enrichment results highlight potential links with chronic inflammation, the hypothalamic-pituitary-adrenal pathway, mitophagy, disrupted vesicle-trafficking, calcium-dependent, and autophagic pathways. Investigations for putative causal genetic effects suggest that a larger putamen volume could influence PD risk, independently of the potential causal genetic effects of intracranial volume (ICV) on PD. Our findings suggest that genetic variants influencing larger intracranial and subcortical brain volumes, possibly during earlier stages of life, influence the risk of developing PD later in life.

Objective: This study aims to describe the establishment of the Mexican Parkinson’s Research Network (MEX-PD), a consortium dedicated to investigating the clinical, genetic, environmental, and neurophysiological underpinnings of phenotypic diversity in Mexican Parkinson’s disease (PD) patients and to present preliminary clinical and genetic outcomes. Methods: PD patients and control participants were recruited from medical centers across Mexico. The initial recruitment phase involved comprehensive neurological evaluations, cognitive assessments, and DNA collection. We conducted classical statistical analyses on clinical variables. Secondly, following genotyping with NeuroBooster array, quality control and imputation, preliminary analysis of ancestry composition, allele frequency calculation and association analysis was carried out for 294 samples. Results: The cohort consisted of 530 control participants and 470 PD patients, with a mean age of diagnosis of 59.9 ± 11.52 years. Among the PD patients, 21.2% were identified as having early-onset PD (<50 years old). Ancestry composition analysis revealed that the main components were European (49.8% in cases and 42.4% in controls) and Native American (46.1% in cases and 54.3% in controls). Variants in genes such as NOTCH , LRRK2 , MTHFR and KPNA1 emerged as relevant to be prioritized in future studies. Conclusions: The MEX-PD consortium will contribute to the understanding of PD within the Mexican population. The data collected will enable a deeper comprehension of the specific contributions of genetic and environmental factors to these outcomes. Significance: This research advocates for the development of personalized treatments and aims to improve the quality of life for Mexican PD patients.

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OBJECTIVE: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population. METHODS: The Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX) and the Mexican Parkinson’s Research Network (Mex-PD) were designed and implemented using Research Electronic Data Capture web-based application. Registries were compiled through voluntary participation and on-site engagement with medical specialists. In some instances, DNA samples and Magnetic Resonance Imaging images were also acquired. RESULTS: Since 2019, the MexOMICS Consortium has successfully established three electronic-based registries: TwinsMX (n=2915), LupusRGMX (n=1761) and Mex-PD (n=750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected samples for genetic determinations across the three registries. Cognitive function assessments, conducted using the Montreal Cognitive Assessment, have been administered to a subsample of 376 Mex-PD participants. Furthermore, a subset of 267 twins underwent measurements of structural, functional, and spectroscopy brain images; comparable evaluations are projected for LupusRGMX and Mex-PD. CONCLUSIONS: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.