MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients

Tolosa, Eduard; Botta-Orfila, Teresa; Morató, Xavier; Calatayud, Carles; Ferrer-Lorente, Raquel; Martí, María‐José; Fernández, Manel; Gaig, Carles; Raya, Ángel; Consiglio, Antonella; Ezquerra, Mario; Fernández‐Santiago, Rubén

doi:10.1016/j.neurobiolaging.2018.05.032

Cited by 62 publications

(34 citation statements)

References 52 publications

(74 reference statements)

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“…MiRNAs were a glass of critical factors that participated in cell proliferation as well as apoptosis [33]. A study has shown miR-199a-5p is strikingly declined in PD [13]. Moreover, a study explained that miR-199a suppressed HIF-1a level under hypoxic environment [34].…”

Section: Discussionmentioning

confidence: 99%

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Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Yang

Kong

2020

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells. Methods: The PC12 cells were incubated by hydrogen peroxide (H 2 O 2) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1a expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1a was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/b-catenin pathways was tested by western blot. Results: Dex attenuated H 2 O 2-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1a expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3 0-UTR of HIF-1a. In addition, Dex activated PI3K/AKT/mTOR and Wnt/b-catenin pathways by declining miR-199a level. Conclusions: This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/ HIF-1a.

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Section: Discussionmentioning

confidence: 99%

“…The decline of miR-101a level accelerated the progress of AD [12]. Moreover, a study showed that the decline of miR-199a-5p, as well as miR-199a-3p levels, was involved in PD [13]. In addition, only a few studies have illustrated miR-199a is closely related to hypoxia-adaptation [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Yang

Kong

2020

Artificial Cells, Nanomedicine, and Biotechnology

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“…By contrast, pivotal PD proteins encoded by genes whose mutations were linked to PD were demonstrated to impact on canonical Wnt/β-catenin signaling [67,68,69] and to inhibit the ability of human induced pluripotent stem cells (iPSCs) to differentiate into DAergic neurons [70], whereas pharmacological Wnt activation restored their mDAergic developmental potential [70]. With the emerging role of micro-RNA (miRNA) regulatory functions on major pathways involved in mDAergic neurodegeneration in PD [71,72,73], patient-specific dysregulation of messenger RNA (mRNA)/miRNA expression is being revealed in PD [74], with an expected impact on Wnt signaling [43,75,76].…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease

Marchetti

2018

IJMS

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Wingless-type mouse mammary tumor virus (MMTV) integration site (Wnt) signaling is one of the most critical pathways in developing and adult tissues. In the brain, Wnt signaling contributes to different neurodevelopmental aspects ranging from differentiation to axonal extension, synapse formation, neurogenesis, and neuroprotection. Canonical Wnt signaling is mediated mainly by the multifunctional β-catenin protein which is a potent co-activator of transcription factors such as lymphoid enhancer factor (LEF) and T-cell factor (TCF). Accumulating evidence points to dysregulation of Wnt/β-catenin signaling in major neurodegenerative disorders. This review highlights a Wnt/β-catenin/glial connection in Parkinson’s disease (PD), the most common movement disorder characterized by the selective death of midbrain dopaminergic (mDAergic) neuronal cell bodies in the subtantia nigra pars compacta (SNpc) and gliosis. Major findings of the last decade document that Wnt/β-catenin signaling in partnership with glial cells is critically involved in each step and at every level in the regulation of nigrostriatal DAergic neuronal health, protection, and regeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, focusing on Wnt/β-catenin signaling to boost a full neurorestorative program in PD.

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“…Patient-derived induced pluripotent stem cells (iPSCs) differentiated to specific neuronal populations have been implemented as a human cell model to study biochemical and molecular aspects of neurodegeneration [262,263]. However, differentiation protocols are challenging [262] and cultured neurons in artificial media may present differences in ncRNA expression and the regulation of OS.…”

Section: Discussionmentioning

confidence: 99%

Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases

et al. 2020

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Oxidative stress (OS) results from an imbalance between the production of reactive oxygen species and the cellular antioxidant capacity. OS plays a central role in neurodegenerative diseases, where the progressive accumulation of reactive oxygen species induces mitochondrial dysfunction, protein aggregation and inflammation. Regulatory non-protein-coding RNAs (ncRNAs) are essential transcriptional and post-transcriptional gene expression controllers, showing a highly regulated expression in space (cell types), time (developmental and ageing processes) and response to specific stimuli. These dynamic changes shape signaling pathways that are critical for the developmental processes of the nervous system and brain cell homeostasis. Diverse classes of ncRNAs have been involved in the cell response to OS and have been targeted in therapeutic designs. The perturbed expression of ncRNAs has been shown in human neurodegenerative diseases, with these changes contributing to pathogenic mechanisms, including OS and associated toxicity. In the present review, we summarize existing literature linking OS, neurodegeneration and ncRNA function. We provide evidences for the central role of OS in age-related neurodegenerative conditions, recapitulating the main types of regulatory ncRNAs with roles in the normal function of the nervous system and summarizing up-to-date information on ncRNA deregulation with a direct impact on OS associated with major neurodegenerative conditions.

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MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients

Cited by 62 publications

References 52 publications

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease

Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases

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