microRNAs in CNS Disorders

Abstract. MicroRNAs (miRNAs) are small, endogenous, non-coding RNA molecules that function as post-transcriptional regulators of gene expression by imperfect base-pairing with the 3'-untranslated regions of their target mRNAs. Altered expression of numerous miRNAs has been shown to be extensively involved in the pathogenesis of various diseases and cancers. Additionally, the specific expression of miRNAs in the nervous system has indicated that miRNAs are critical for the occurrence and development of neurological diseases. Increasing evidence has shown that specific miRNAs target the expression of particular proteins that are significant in the disease pathogenesis. Therefore, miRNA-mediated regulation may be important in the occurrence and development of neurological diseases and may function as a novel biomarker and tool for clinical therapy. In the present study, the significance of miRNAs is reviewed in a number of neurological disorders and the possibility of their use in therapeutic interventions is evaluated.

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“…Previous studies have shown that stroke also induces changes in the miRNA expression profiles in rodents, as well as humans (30,31) (Table I).…”

Section: Strokementioning

confidence: 90%

Neuroprotection of microRNA in neurological disorders (Review)

Wang

Cheng

et al. 2014

Biomedical Reports

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“…There are over 1000 miRNAs in humans and they are typically measured using either RNA sequencing, microarray, Nanostring, or real-time quantitative polymerase chain reaction methodologies. Alterations in miRNA regulation has been implicated in a wide variety of CNS disorders [110][111][112]. Defects in miRNA biogenesis, for example via knockout of Dicer, has been correlated with decreased motor activity and survival, muscle atrophy, denervation, spinal cord sclerosis, and axonopathy in mice [113].…”

Section: Micrornamentioning

confidence: 99%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

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“…Several downregulated miRNAs have been demonstrated in the brain, including the miR-107 (9) and miR-29 families (5), which regulate the expression of BACE1 and consequently affect the production of Aβ. Of the presently identified miRNAs, ~70% are expressed in the brain, however, the pathological implications of dysregulated miRNA expression in AD remain to be fully elucidated (10).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang

Song

Zhou

et al. 2015

Molecular Medicine Reports

101

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Abstract. Alzheimer's disease (AD), characterized by β-amyloid deposition and neurodegeneration, is the most common cause of dementia worldwide. Emerging evidence suggests that ectopic expression of micro (mi)RNAs is involved in the pathogenesis of AD. There is increasing evidence that miRNAs expressed in the brain are involved in neuronal development, survival and apoptosis. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is regulated by dysregulated miRNAs in the brain. The present study determined the expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of patients with AD and demonstrated a marked decrease in the expression of miR-29c compared with age-matched controls. In addition, a significant increase in the exprssion of BACE1 was observed in the peripheral blood of patients with AD. Correlation analysis revealed that the expression of miR-29c was negatively correlated with the protein expression of BACE1 in the peripheral blood samples from patients with AD. The present study also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. The results demonstrated that the upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at least partially, by increasing the activity of protein kinase A/cAMP response element-binding protein, involved in neuroprotection. This evidence suggested that miR-29c may be a promising potential therapeutic target against AD.

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microRNAs in CNS Disorders

Cited by 75 publications

References 77 publications

Neuroprotection of microRNA in neurological disorders (Review)

Neuroprotection of microRNA in neurological disorders (Review)

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

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