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OBJECTIVE: This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. METHODS: Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. RESULTS: Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. CONCLUSION: Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.

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Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

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Tumoral microRNAs, such as miR-125b and miR-155b, are important gene expression regulators with complex pathogenetic mechanisms. However, their role in DLBCL, especially when cell-of-origin classification is considered, are still to be elucidated. In a series of 139 DLBCL cases considering germinal center (GC) versus nonGC subtypes, we investigated miR-125b and miR-155b expression by in situ hibridization and their association with some immunophenotypic presentations, including MYC, BCL2 and TP53 expression, MYC, BCL2 and BCL6 translocation status, as well as clinicopathological features and outcomes. miR-125b detection was positively correlated to the Ki-67 index (P = 0.035) in the nGC. Considering the GC subgroup, the percentage of miR-125b positive cells was also correlated to either MYC and MYC/BCL2 double expression (P = 0.047 and P = 0.049, respectively). When it comes to nGC patients, miR-155b percentage and intensity, as well as Allred score, were positively correlated to disease progression (P = 0.038, P = 0.057 and P = 0.039, respectively). In a multivariate analysis, GC phenotype was a significant independent factor associated with higher OS (P = 0.007) and, considering the nGC group, although not significant, the expression of TP53, miR-125b and miR-155b seems to be potential prognostic biomarkers in these tumors. This study demonstrated different pathways based on cell-of-origin classification and highlighted different clinical outcomes. miR-125b, miR-155b and TP53 expression may also represent potential prognostic factors in nGC-DLBCL.

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MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene regulation. They function by binding to target messenger RNA (mRNA) molecules, leading to their degradation or inhibiting their translation into proteins. In the context of skeletal diseases, such as osteoporosis, osteoarthritis, and bone metastasis, there is growing evidence osteoblastic miRNAs, are involved in the regulation of bone formation and maintenance.Osteoblasts are bone-forming cells responsible for synthesizing and depositing the extracellular matrix, which ultimately mineralizes to form bone tissue. Osteoblastic miRNAs modulate various aspects of osteoblast function, including proliferation, differentiation, mineralization, and apoptosis. Dysregulation of these miRNAs can disrupt the balance between bone formation and resorption, leading to skeletal diseases.The therapeutic implications of targeting osteoblastic miRNAs in skeletal diseases are significant. Modulating the expression levels of specific miRNAs holds promise for developing novel therapeutic strategies to enhance bone formation, prevent bone loss, and promote bone regeneration. Potential therapeutic approaches include the use of synthetic miRNA mimics to restore miRNA expression in diseases associated with miRNA downregulation or the use of anti-miRNA oligonucleotides to inhibit miRNA function in diseases associated with miRNA upregulation.miRNA-based therapies are still in the early stages of development, and further research is needed to fully understand the complexity of miRNA networks. Additionally, the delivery of miRNAs to specific target tissues and cells remains a challenge that needs to be addressed for effective clinical translation. Nonetheless, targeting osteoblastic miRNAs represents a promising avenue for future therapeutic interventions in skeletal diseases. (AU)

Los micro-ARNs (miARNss) son pequeños ARN no codificantes que desempeñan un papel fundamental en la regulación génica postranscripcional. Ejercen su función al unir-se a moléculas de ARN mensajero (ARNm), promoviendo su degradación e inhibiendo su traducción en proteínas. En el contexto de las enfermedades esqueléticas, como la osteoporosis, la osteoartritis y la metástasis ósea existe evidencia de que los miARNs osteoblásticos están involucrados en la regulación de la formación y del mantenimiento óseo. Los osteoblastos son células formadoras de hueso responsables de sintetizar y depositar la matriz extracelular, que finalmente se mineraliza para formar el hueso. Los miARNs derivados de osteoblastos modulan varios aspectos de la función de estas células, incluida la proliferación, diferenciación, mineralización y la apoptosis. La desregulación de estos miARNs puede alterar el equilibrio entre la formación y la resorción ósea, lo que lleva a enfermedades óseas. Las implicaciones terapéuticas de los miARNs osteoblásticos en enfermedades esqueléticas son significativas. La modulación de los niveles de expresión de miARNs específicos es prometedora para desarrollar nuevas estrate-gias terapéuticas a fin de mejorar la formación, prevenir la pérdida y promover la regeneración ósea. Los enfoques terapéuticos potenciales incluyen el uso de miméticos de miARNs para restaurar la expresión de miARNs o el uso de oligonucleótidos anti-miARNs para inhibir su función. Las terapias basadas en miARNs aún se encuentran en las primeras etapas de desarrollo. La administración de miARNs a las células y los tejidos específicos sigue siendo un desafío para lograr una aplicación clínica eficaz. (AU)

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Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is trans-chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the trans-chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18 µM, respectively. Subsequently, we treated MCF-7 cells with trans-chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy.

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Leukemia is a type of cancer that affects white blood cells. In this disease, immature blood cells undergo genetic mutations, leading to excessive replication and reduced cell death compared to healthy cells. In cancer, there may be the activation of oncogenes and the deactivation of tumor suppressor genes that control certain cellular functions. Despite the undeniable contribution to the patient's recovery, conventional cancer treatments may have some not-so-beneficial effects. In this case, gene therapy appears as an alternative to classical treatments. Gene therapy delivers genetic material to cells to replace or modify dysfunctional genes, a safe method for neoplasms. One of the types of nucleic acids explored in gene therapy is microRNA (miRNA), a group of endogenous, non-proteincoding, small single-stranded RNA molecules involved in the regulation of gene expression, cell division, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. This review aims to bring together the most recent advances found in the literature on cancer gene therapy based on microRNAs in the oncological context, focusing on leukemia.

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Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers (BC) in the US and its diagnosis is associated with poor survival outcomes. A better understanding of the disease etiology is crucial to identify target treatment options to improve patient outcomes. The role of exo-miRNAs in TNBC has been studied for more than two decades. Although some studies have identified exo-miR candidates in TNBC using clinical samples, consensus regarding exo-miR candidates has not been achieved. The purpose of this review is to gather information regarding exo-miR candidates reported in TNBC translational studies along with the techniques used to isolate and validate the potential targets. The techniques suggested in this review are based on the use of commercially available materials for research and clinical laboratories. We expect that the information included in this review can add additional value to the recent efforts in the development of a liquid biopsy to identify TNBC cases and further improve their survival outcomes.

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Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.

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MicroRNAs (miRNAs) are small (~21 nucleotides) endogenous noncoding RNA molecules involved in the posttranscriptional regulation of gene expression. Modulation of gene expression by miRNAs occurs via base-pairing of the specific miRNA primary sequence to its corresponding target messenger RNA, which can be located either in the 3' untranslated region or within the coding sequence. This pairing can lead to either translational repression or cleavage of the mRNA, resulting in reduced levels of the target protein. MiRNAs are involved in mediating and controlling several interactions between immune and cancer cells and are also important regulators of immune responses. Increasing interest has focused on elucidating the role of miRNAs in the regulation of anticancer immune responses and how this could affect the efficacy of different cancer therapeutics. Indeed, immune responses have both pro- and anti-oncogenic effects, and functional interactions between immune and cancer cells in the tumor microenvironment are crucial in determining the course of cancer progression. Thus, understanding the role of miRNAs in controlling cancer immunity is important for revealing mechanisms that could be modulated to enhance the success of immunotherapy for patients with cancer. In this chapter, we discuss the involvement of miRNAs in the regulation of immune cells and potential therapeutic approaches in which miRNAs are used for cancer immunotherapy.

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Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly's tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.

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microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

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Visceral leishmaniasis in humans is a chronic and fatal disease if left untreated. Canine leishmaniasis (CanL) is a severe public health problem because infected animals are powerful transmitters of the parasite to humans via phlebotomine vectors. Therefore, dogs are an essential target for control measures. Progression of canine infection is accompanied by failure of cellular immunity with reduction of circulating lymphocytes and increased cytokines that suppress macrophage function. Studies showed that the regulation of the effector function of macrophages and T cells appears to depend on miRNAs; miRNA-21 (miR-21) shows increased expression in splenic leukocytes of dogs with CanL and targets genes related to the immune response. Mimics and inhibitors of miR-21 were used in vitro to transfect splenic leukocytes from dogs with CanL. After transfection, expression levels of the proteins FAS, FASL, CD69, CCR7, TNF-α, IL-17, IFN-γ, and IL-10 were measured. FAS, FASL, CD69, and CCR7 expression levels decreased in splenic leukocytes from dogs with CanL. The miR-21 mimic decreased CD69 expression in splenic leukocytes from CanL and healthy groups. The miR-21 inhibitor decreased IL-10 levels in culture supernatants from splenic leukocytes in the CanL group. These findings suggest that miR-21 alters the immune response in CanL; therefore, miR-21 could be used as a possible therapeutic target for CanL.

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Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing ß-cells leading to impaired insulin secretion and hyperglycemia. T1D is accompanied by DNA damage, oxidative stress, and inflammation, although there is still scarce information about the oxidative stress response and DNA repair in T1D pathogenesis. We used the microarray method to assess mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of 19 T1D patients compared to 11 controls and identify mRNA targets of microRNAs that were previously reported for T1D patients. We found 277 differentially expressed genes (220 upregulated and 57 downregulated) in T1D patients compared to controls. Analysis by gene sets (GSA and GSEA) showed an upregulation of processes linked to ROS generation, oxidative stress, inflammation, cell death, ER stress, and DNA repair in T1D patients. Besides, genes related to oxidative stress responses and DNA repair (PTGS2, ATF3, FOSB, DUSP1, and TNFAIP3) were found to be targets of four microRNAs (hsa-miR-101, hsa-miR148a, hsa-miR-27b, and hsa-miR-424). The expression levels of these mRNAs and microRNAs were confirmed by qRT-PCR. Therefore, the present study on differential expression profiles indicates relevant biological functions related to oxidative stress response, DNA repair, inflammation, and apoptosis in PBMCs of T1D patients relative to controls. We also report new insights regarding microRNA-mRNA interactions, which may play important roles in the T1D pathogenesis.

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Although the study of ribonucleic acid (RNA) therapeutics started decades ago, for many years, this field of research was overshadowed by the growing interest in DNA-based therapies. Nowadays, the role of several types of RNA in cell regulation processes and the development of various diseases have been elucidated, and research in RNA therapeutics is back with force. This short literature review aims to present general aspects of many of the molecules currently used in RNA therapeutics, including in vitro transcribed mRNA (IVT mRNA), antisense oligonucleotides (ASOs), aptamers, small interfering RNAs (siRNAs), and microRNAs (miRNAs). In addition, we describe the state of the art of technologies applied for synthetic RNA manufacture and delivery. Likewise, we detail the RNA-based therapies approved by the FDA so far, as well as the ongoing clinical investigations. As a final point, we highlight the current and potential advantages of working on RNA-based therapeutics and how these could lead to a new era of accessible and personalized healthcare.

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MicroRNAs (miRNAs) are small non-coding RNA molecules able to post-transcriptionally regulate gene expression via base-pairing with partially complementary sequences of target transcripts. Prion diseases comprise a singular group of neurodegenerative conditions caused by endogenous, misfolded pathogenic (prion) proteins, associated with molecular aggregates. In humans, classical prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and kuru. The aim of this review is to present the connections between miRNAs and prions, exploring how the interaction of both molecular actors may help understand the susceptibility, onset, progression, and pathological findings typical of such disorders, as well as the interface with some prion-like disorders, such as Alzheimer's. Additionally, due to the inter-regulation of prions and miRNAs in health and disease, potential biomarkers for non-invasive miRNA-based diagnostics, as well as possible miRNA-based therapies to restore the levels of deregulated miRNAs on prion diseases, are also discussed. Since a cure or effective treatment for prion disorders still pose challenges, miRNA-based therapies emerge as an interesting alternative strategy to tackle such defying medical conditions.

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Micro-RNA-221(miR-221) is one of oncogenic miRNAs that plays a vital role in the development and progression of oral cancers. The aim of this study is to introduce a new gene therapy for oral squamous cell carcinoma by blocking the expression of oncogenic miR-221 by its inhibitor. The present work was performed on squamous cell carcinoma cell line SCC-25 and anti-miR-221 was delivered to the cells using an ultrasound micro bubbles. Assessment of the effect of miR-221 inhibitor on SCC-25 cells was done using MTT assay, cell cycle analysis and apoptosis detection. In addition, reverse transcription-polymerase chain reaction was also used to detect the expression -miR-221 and its target genes. Using ANOVA, statistical analysis of the results showed significant inhibition of cell viability with and induction of cell apoptosis of SCC-25 cell line after transfection. Moreover, the expression of miR-221, Epidermal growth factor receptor (EGFR) and CDKNIB/p27 were downregulated without significant difference. Transfection of SCC-25 by inhibitor of miR-221 resulting in blockage of its expression leading to arresting of tumor growth. These results proved the effective role of micro-RNA inhibitors as novel therapeutic agent for oral cancers.

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Abstract Micro-RNA-221(miR-221) is one of oncogenic miRNAs that plays a vital role in the development and progression of oral cancers. The aim of this study is to introduce a new gene therapy for oral squamous cell carcinoma by blocking the expression of oncogenic miR-221 by its inhibitor. The present work was performed on squamous cell carcinoma cell line SCC-25 and anti-miR-221 was delivered to the cells using an ultrasound micro bubbles. Assessment of the effect of miR-221 inhibitor on SCC-25 cells was done using MTT assay, cell cycle analysis and apoptosis detection. In addition, reverse transcription-polymerase chain reaction was also used to detect the expression -miR-221 and its target genes. Using ANOVA, statistical analysis of the results showed significant inhibition of cell viability with and induction of cell apoptosis of SCC-25 cell line after transfection. Moreover, the expression of miR-221, Epidermal growth factor receptor (EGFR) and CDKNIB/p27 were downregulated without significant difference. Transfection of SCC-25 by inhibitor of miR-221 resulting in blockage of its expression leading to arresting of tumor growth. These results proved the effective role of micro-RNA inhibitors as novel therapeutic agent for oral cancers.

Resumo Micro-RNA-221 (miR-221) é um dos miRNAs oncogênicos que desempenham um papel vital no desenvolvimento e progressão de carcinomas orais. O objetivo deste estudo é apresentar uma nova terapia gênica para o carcinoma epidermóide oral por meio do bloqueio da expressão do miR-221 oncogênico por seu inibidor. O presente trabalho foi realizado na linhagem de células de carcinoma de células escamosas SCC-25 e o anti-miR-221 foi administrado às células usando micro-bolhas de ultrassom. A avaliação do efeito do inibidor miR-221 em células SCC-25 foi feita usando ensaio de MTT, análise do ciclo celular e detecção de apoptose. Além disso, a reação em cadeia da polimerase com transcrição reversa também foi usada para detectar a expressão -miR-221 e seus genes-alvo. Usando ANOVA, a análise estatística dos resultados mostrou inibição significativa da viabilidade celular e indução da apoptose celular da linhagem celular SCC-25 após a transfecção. Além disso, a expressão de miR-221, receptor do fator de crescimento epidérmico (EGFR) e CDKNIB/p27 foram regulados para baixo sem diferença significativa. A transfecção de SCC-25 por inibidor de miR-221 resultou no bloqueio de sua expressão, levando à interrupção do crescimento do tumor. Esses resultados comprovaram o papel eficaz dos inibidores de micro-RNA como novo agente terapêutico para carcinomas orais.

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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.

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MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3'-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson's disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression -a neuroprotective agent-remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics.

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MicroRNAs (miRNAs) are short, endogenous, noncoding RNAs that regulate gene expression through posttranscriptional mechanisms via degradation or inhibition of specific mRNAs targets. In recent years, abundant studies have illustrated the relevance of miRNAs in human psychopathology. In this current review, neuropsychiatric disorders with moderate to high prevalence among children and adolescents such as Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, Dyslexia, Epilepsy, Schizophrenia and Tourette Syndrome were discussed focusing on the functional consequence of altered miRNA expression during the development of such diseases. The insight about the roles that miRNAs play in central nervous systems development such as cell proliferation and differentiation, synaptogenesis, synaptic plasticity, and apoptosis might be the key to explicate novel biomarkers for diagnosis and prognosis of these disorders, as well as the finding of new targets for drug development for therapeutic approaches.

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