scholarly journals MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment

Author(s):  
Mona Hussein ◽  
Rehab Magdy

AbstractMicroRNAs (miRNAs) are a class of short, non-coding, regulatory RNA molecules that function as post transcriptional regulators of gene expression. Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease. miRNAs are implicated in the pathogenesis of excitotoxicity, apoptosis, oxidative stress, inflammation, neurogenesis, angiogenesis, and blood–brain barrier protection. Consequently, miRNAs can serve as biomarkers for different neurological disorders. In recent years, advances in the miRNA field led to identification of potentially novel prospects in the development of new therapies for incurable CNS disorders. MiRNA-based therapeutics include miRNA mimics and inhibitors that can decrease or increase the expression of target genes. Better understanding of the mechanisms by which miRNAs are implicated in the pathogenesis of neurological disorders may provide novel targets to researchers for innovative therapeutic strategies.

2019 ◽  
Vol 101 (6) ◽  
pp. 1167-1178 ◽  
Author(s):  
Sarah Bjorkman ◽  
Hugh S Taylor

AbstractMicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.


Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 165
Author(s):  
Laura R. Rodríguez ◽  
Tamara Lapeña-Luzón ◽  
Noelia Benetó ◽  
Vicent Beltran-Beltran ◽  
Federico V. Pallardó ◽  
...  

Calcium (Ca2+) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca2+ homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca2+ exchange is mediated by appositions, termed endoplasmic reticulum–mitochondria-associated membranes (MAMs), formed by proteins resident in both compartments. These tethers are essential to manage the mitochondrial Ca2+ influx that regulates the mitochondrial function of bioenergetics, mitochondrial dynamics, cell death, and oxidative stress. However, alterations of these pathways lead to the development of multiple human diseases, including neurological disorders, such as amyotrophic lateral sclerosis, Friedreich’s ataxia, and Charcot–Marie–Tooth. A common hallmark in these disorders is mitochondrial dysfunction, associated with abnormal mitochondrial Ca2+ handling that contributes to neurodegeneration. In this work, we highlight the importance of Ca2+ signaling in mitochondria and how the mechanism of communication in MAMs is pivotal for mitochondrial maintenance and cell homeostasis. Lately, we outstand potential targets located in MAMs by addressing different therapeutic strategies focused on restoring mitochondrial Ca2+ uptake as an emergent approach for neurological diseases.


2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.


2020 ◽  
Vol 13 (2) ◽  
pp. 85-93
Author(s):  
Kinjal Gangar ◽  
Lokesh Kumar Bhatt

One of the most common neurological disorders, which occurs among 1% of the population worldwide, is epilepsy. Therapeutic failure is common with epilepsy and nearly about 30% of patients fall in this category. Seizure suppression should not be the only goal while treating epilepsy but associated comorbidities, which can further worsen the condition, should also be considered. Treatment of such comorbidities such as depression, anxiety, cognition, attention deficit hyperactivity disorder and, various other disorders which co-exist with epilepsy or are caused due to epilepsy should also be treated. Novel targets or the existing targets are needed to be explored for the dual mechanism which can suppress both the disease and the comorbidity. New therapeutic targets such as IDO, nNOS, PAR1, NF-κb are being explored for their role in epilepsy and various comorbidities. This review explores recent therapeutic targets for the treatment of comorbidities associated with epilepsy.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.


Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fulu Dong ◽  
Yuan Zhang ◽  
Fei Xia ◽  
Yi Yang ◽  
Sidong Xiong ◽  
...  

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Amir Hossein Hasani Fard ◽  
Hanieh Jalali ◽  
Homa Mohseni Kouchesfehani

Background: Cholestasis is a pathophysiological condition, significantly reducing spermatozoa production. MiR-34c is highly expressed in adult male testicles and controls different stages of spermatogenesis. Objectives: Here, we aimed to investigate miR-34c expression in the testes of rat models of cholestasis. The expressions of THY-1, FGF-2, and CASP-3 genes, that are targeted by mirR-34c were also investigated. Methods: Cholestasis was induced in six adult rats via bile duct ligation. Four weeks after cholestasis induction, sera and testicular tissues were collected for further examinations. The levels of liver enzymes were measured using the ELISA. The structure of the testes was evaluated by histological examination. Total RNA was extracted from testes using a special kit and converted to cDNA. The expressions of miR-34c-5p, THY-1, FGF-2, and CASP-3 genes were determined by Real-Time PCR. Results: The serum levels of ALP, AST, and ALT were significantly elevated in the rat models of cholestasis (P < 0.001). Real-Time PCR revealed that the expressions of miR-34c-5p, THY-1, and FGF-2 genes decreased while CASP-3 gene was upregulated in the testes of cholestatic animals (all differences were significant at P < 0.05). Conclusions: Our study indicated that cholestasis was associated with reduced expression of miR-34c and altered expression of its target genes in the testis. Our results highlight the potential effects of cholestasis, a hepatobiliary disease, on testicular tissue function and male fertility.


2010 ◽  
Vol 86 (3) ◽  
pp. 353-364 ◽  
Author(s):  
W. Poller ◽  
R. Hajjar ◽  
H. P. Schultheiss ◽  
H. Fechner

Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 263-271 ◽  
Author(s):  
Maryam Kiani ◽  
Mohammad Salehi ◽  
Asghar Mogheiseh

SummaryInfertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.


Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson&rsquo;s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington&rsquo;s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.


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