MicroRNAs in Neurodegenerative Diseases

Quinlan, Sean; Kenny, Aidan; Medina, Miguel; Engel, Tobías; Jiménez-Mateos, Eva M.

doi:10.1016/bs.ircmb.2017.04.002

Cited by 147 publications

(101 citation statements)

References 133 publications

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“…The availability of biomarkers to assess the appearance and progression of PD is fundamental to perform an early therapeutic intervention as well as to monitor the clinical response. So far there are several leading biomarker candidates including α-SYN (Atik et al, 2016), image biomarkers (Saeed et al, 2017), LRRK2 (Taymans et al, 2017), and microRNAs (Quinlan et al, 2017;Khodadadian et al, 2018).…”

Section: Precision Medicine In a Preventive Approachmentioning

confidence: 99%

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Iarkov

Barreto

Grizzell

et al. 2020

Front. Aging Neurosci.

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Parkinson's disease (PD) is the second-leading cause of dementia and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra alongside the presence of intraneuronal α-synuclein-positive inclusions. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. Thus, the development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD.

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Section: Precision Medicine In a Preventive Approachmentioning

confidence: 99%

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Iarkov

Barreto

Grizzell

et al. 2020

Front. Aging Neurosci.

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“…Over the years, expression profiling of miRNAs associated with AD has been performed in the brain tissues, cerebrospinal fluid, and blood of AD patients and transgenic AD mouse models. Although several miRNAs have been identified in AD, an understanding of the role of miRNA in human AD is still limited (Tan et al, 2013;Maoz et al, 2017;Quinlan et al, 2017). miRNAs may be involved in AD pathogenesis via multiple pathways, such as APP formation, phosphorylation of tau protein, and synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Loss of miR-369 Promotes Tau Phosphorylation by Targeting the Fyn and Serine/Threonine-Protein Kinase 2 Signaling Pathways in Alzheimer’s Disease Mice

Yao

Xia

Fang

et al. 2020

Front. Aging Neurosci.

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Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative dementia with the key pathological hallmarks amyloid-beta deposition and neurofibrillary tangles composed of hyperphosphorylated tau. microRNAs (miRNAs) are small non-coding RNAs that contribute to the pathogenesis of AD. In this study, we investigated the effect of the loss of miR-369 on the phosphorylation of tau protein and the activation of the kinases Fyn and serine/threonine-protein kinase 2 (SRPK2) as the upstream molecules facilitating tau phosphorylation in miR-369 knockout 3xTg-AD mice.Methods: We generated miR-369 knockout 3xTg-AD mice and investigated their cognitive behaviors by maze tests. Real-time qPCR, western blot, and immunohistochemistry were performed to evaluate the expression of the miR-369 gene, phosphorylation of tau protein, and activation of Fyn and SRPK2. Luciferase reporter assays were applied to confirm the predicted targets of miR-369.Results: Knocking out miR-369 in 3xTg AD mice aggravated cognitive impairment, promoted hyperphosphorylation of tau, and upregulated Fyn and SRPK2. Restoring miR-369 reversed the hyperphosphorylation of tau and downregulated Fyn and SRPK2. Additionally, miR-369 was shown to target the 3 UTRs of Fyn and SRPK2 to regulate their expression levels.Conclusion: Loss of miR-369 promotes tau phosphorylation by targeting the Fyn and SRPK2 signaling pathways in AD mice, and supplementation with miR-369 might be a valuable option for AD therapeutic studies.

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“…This disease is the second most common neurodegenerative disorder following Alzheimer disease (1). Current evidence suggests that miRs are involved in diverse biological processes including pathogenesis of neurodegenerative disorders and abnormal brain function (8,14). With regard to PD, several miRs have been reported to participate and play important roles in PD progression, via the regulation of various processes, such as apoptosis, autophagy, inflammation, mitochondrial dysfunction, and ROS activity (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…By binding directly to the 3'-UTR (3'-untranslated region) of target mRNAs, miRNAs are involved in a series of physiological and pathological processes (6). Accumulating evidence suggests that the dysregulation of miRNA plays an important role in the pathogenesis of neurodegenerative disorders, including PD (7,8). Fu et al (9) demonstrated that docosahexaenoic acid upregulated the expression of Peroxisome Proliferator Activated Receptor α by inhibiting miR-21 in SH-Y5Y cells.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑21 suppresses 1‑methyl‑4‑phenylpyridinium‑induced neuronal damage in MES23.5 cells

Mao

Ding

2019

Exp Ther Med

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Accumulating evidence suggests that overproduction of oxidative stress, increases neuroinflammation and activates apoptosis. These two processes are associated with the development of Parkinson's disease (PD). The present study aimed to investigate the role of miR-21 in the development of PD. 1-Methyl-4-phenylpyridinium (MPP + ) was used to induce a PD-like model in MES23.5 cells. The results of the reverse transcription-quantitative PCR assays indicated that miR-21 levels were markedly increased in MES23.5 cells following MPP + treatment. Furthermore, MES23.5 cells were transfected with miR-21 inhibitor, mimics and/ or relevant negative control, following MPP + administration. The results of the functional assays revealed that downregulation of miR-21 significantly attenuated the induction of cell apoptosis and reactive oxygen species (ROS) production, while it enhanced the survival of MPP + -induced MES23.5 cells. Furthermore, downregulation of miR-21 increased the expression levels of tyrosine hydroxylase, whereas suppression of miR-21 inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, IL-1β and tumor necrosis factor-α] in MES23.5 cells. Western blot analysis further indicated that the Bcl-2/Bax protein expression ratio was significantly increased and double luciferase assay analysis confirmed that Bcl-2 was a direct target of miR-21. Taken collectively, the data demonstrated that downregulation of miR-21 protected cells from MPP + -mediated cytotoxicity by the inhibition of apoptosis induction, the reduction of the inflammatory response and the suppression of ROS production. The present findings may provide novel approaches for PD clinical treatment.

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MicroRNAs in Neurodegenerative Diseases

Cited by 147 publications

References 133 publications

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Loss of miR-369 Promotes Tau Phosphorylation by Targeting the Fyn and Serine/Threonine-Protein Kinase 2 Signaling Pathways in Alzheimer’s Disease Mice

Downregulation of miR‑21 suppresses 1‑methyl‑4‑phenylpyridinium‑induced neuronal damage in MES23.5 cells

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