microRNA‐221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease

Yao, Yu-Fang; Zhao, Zhengyan; Zhang, Fubo; Miao, Na; Wang, Nan; Xu, Xin; Yang, Chao-Ping

doi:10.1002/brb3.2921

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…In this regard, a piece of evidence reported that miRNAs are involved in the regulation of DA-ergic circuits, α-Syn production and animal behavior. For instance, in the PD animal model 6-OHDA, the overexpression of miR-221 -usually downregulated in patients, improved motor behavior targeting the Bim/Bax/caspase-3 signaling axis, known to be involved in the apoptosis of DA-ergic cells in SN (Yao et al, 2023). In the same PD model, the overexpression of miR-375 reduces DAergic damage, oxidative stress and inflammation, by the inhibition of transcription factor specificity protein 1 (Cai et al, 2020).…”

Section: Ncrna As Biomarkers and Therapeutic Target In Pdmentioning

confidence: 99%

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

Meccariello,

Bellenchi,

Pulcrano

et al. 2024

Front. Cell. Neurosci.

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Over the last few decades, emerging evidence suggests that non-coding RNAs (ncRNAs) including long-non-coding RNA (lncRNA), microRNA (miRNA) and circular-RNA (circRNA) contribute to the molecular events underlying progressive neuronal degeneration, and a plethora of ncRNAs have been identified significantly misregulated in many neurodegenerative diseases, including Parkinson’s disease and synucleinopathy. Although a direct link between neuropathology and causative candidates has not been clearly established in many cases, the contribution of ncRNAs to the molecular processes leading to cellular dysfunction observed in neurodegenerative diseases has been addressed, suggesting that they may play a role in the pathophysiology of these diseases. Aim of the present Review is to overview and discuss recent literature focused on the role of RNA-based mechanisms involved in different aspects of neuronal pathology in Parkinson’s disease and synucleinopathy models.

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Section: Ncrna As Biomarkers and Therapeutic Target In Pdmentioning

confidence: 99%

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

Meccariello,

Bellenchi,

Pulcrano

et al. 2024

Front. Cell. Neurosci.

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“…In PD, the expression of Bim is controlled by the activation of the JNK/c‐jun signalling pathway and the decrease in its translocation to the mitochondrial field (Hu et al, 2019). Based on Yao et al (2023) study, there was a notable decrease in miR‐221 levels in the blood of PD patients and brain tissue of mice with a chemically induced form of the disease. The study showed that introducing additional miR‐221 prevented the death of dopamine‐producing neurons in the mice and also influenced the Bax/caspase‐3 pathway by interacting with Bim.…”

Section: The Neuroprotective Role Of Mir‐221 In Pd: Insights From In ...mentioning

confidence: 99%

miR‐221 and Parkinson's disease: A biomarker with therapeutic potential

Zamanian,

Ivraghi,

Gupta

et al. 2023

Eur J of Neuroscience

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non‐motor symptoms. Several cellular and molecular mechanisms such as alpha‐synuclein (α‐syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post‐transcriptional gene regulation. They are typically about 21–25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR‐221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR‐221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR‐221 in PD has been investigated in several studies. According to the results of these studies, (1) miR‐221 protects PC12 cells against oxidative stress induced by 6‐hydroxydopamine; (2) miR‐221 prevents Bax/caspase‐3 signalling activation by stopping Bim; (3) miR‐221 has moderate predictive power for PD; (4) miR‐221 directly targets PTEN, and PTEN over‐expression eliminates the protective action of miR‐221 on p‐AKT expression in PC12 cells; and (5) miRNA‐221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR‐221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.

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microRNA‐221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease

et al. 2023

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Background: Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR-221 in PD. Methods: To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice. Results: Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways. Conclusion: Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.

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microRNA‐221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease

Cited by 4 publications

References 34 publications

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

miR‐221 and Parkinson's disease: A biomarker with therapeutic potential

microRNA‐221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease

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