miR-132-5p regulates apoptosis and autophagy in MPTP model of Parkinson’s disease by targeting ULK1

Zhao, Jianli; Yang, Manyi; Li, Qi; Pei, Xiaorui; Zhu, Xiaodong

doi:10.1097/wnr.0000000000001494

Cited by 22 publications

(8 citation statements)

References 23 publications

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“…of miR-132-5p, which is upregulated in MPTP-induced Pd models, decreases neuronal apoptosis and autophagy via direct targeting of ULK1, suggesting the enhancement of autophagy in miR-132-5p-mediated neurotoxicity in Pd (95). One explanation for this may be that miR-132-5p is involved in MPTP-stimulated overactivation of autophagy in neurons, ultimately leading to autophagic cell death.…”

Section: Neurotoxicity Of Mirnas By Regulating Autophagymentioning

confidence: 99%

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

Ma¹,

Liang²,

Hu³

et al. 2023

Int J Mol Med

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Parkinson's disease (Pd) is a neurodegenerative disorder that has a high incidence during the aging process and is characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunctions and non-motor symptoms. Impaired clearance and excessive accumulation of aberrantly modified proteins or damaged organelles, such as aggregated α-synuclein and dysfunctional mitochondria, are regarded as the main causes of nigrostriatal neurodegeneration. As one of the major degradation pathways, autophagy can recycle these useless or toxic substances to maintain cellular homeostasis and it plays a crucial role in Pd progression. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that regulate gene expression by silencing targeted mRNAs. Recent studies have illustrated that autophagy-regulating miRNA has been implicated in pathological processes of Pd, including α-synuclein accumulation, mitochondrial damage, neuroinflammation and neuronal apoptosis, which suggests that targeting autophagy-regulating miRNAs may provide novel therapeutic strategies for this disease. The present review summarizes the role of autophagy in Pd and emphasizes the role of miRNA-mediated autophagy in Pd, for the development of promising interventions in this disease.

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Section: Neurotoxicity Of Mirnas By Regulating Autophagymentioning

confidence: 99%

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

Ma¹,

Liang²,

Hu³

et al. 2023

Int J Mol Med

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“…Despite of very short half-life (<30 min) of ( R )-ketamine in rodents [ 27 ], ( R )-ketamine can elicit long-lasting (>7 days) prophylactic effects in LPS model [ 44 ] and CRS model [this study]. It is reported that inhibition of miR-132-5p increased cell survival ability and reduced MPTP (1-methyl-4-pheny-1,2,3,6-tetrahydropyridine)-induced apoptosis of SH-SY5Y cells, suggesting that miR-132-5p inhibition may be a potential therapeutic target for Parkinson’s disease [ 63 ]. Collectively, it seems that higher expression of miR-132-5p in the PFC might contribute to depression-like behaviors in CRS-exposed mice, and that inhibition of miR-132-5p could show antidepressant-like effects in CRS-exposed mice.…”

Section: Discussionmentioning

confidence: 99%

A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice

Wang

Chang

et al. 2022

Transl Psychiatry

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Abstract(R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. However, the precise molecular mechanisms underlying its action remain elusive. Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine.

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“…Uridine at the 5′ end of miRNA, which can partially complement the 3′ untranslated region of mRNA, leading to in translation repression of the mRNA, thus, playing a vital role in post-transcriptional regulation of gene expression 60 . Numerous studies have unveiled that multiple mi-RNAs, including miR-372 61 , miR-93 62 , miR-142-5p 63 , miR-20a 64 , 65 , miR-106b 64 , miR-106a 66 , 67 , 68 , miR-26a/b 69 , miR-489 70 , miR-1262 71 , miR-214 72 , miR-214-3p 46 , miR-125b 72 , and miR-155 73 inhibit ULK1 gene expression by directly targeting the mRNA of ULK1 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 . In addition, microRNAs could also play an indirect role by regulating ULK1-related pathways.…”

Section: The Molecular Basis Underlying the Regulation Mechanism Of Ulk1mentioning

confidence: 99%

Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

Zou

Liao

Zhen

et al. 2022

Acta Pharmaceutica Sinica B

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miR-132-5p regulates apoptosis and autophagy in MPTP model of Parkinson’s disease by targeting ULK1

Cited by 22 publications

References 23 publications

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice

Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

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