MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression

Aschrafi, Armaz; Verheijen, Jan; Gordebeke, Peter; Loohuis, Nikkie F. Olde; Menting, Kelly; Jager, Amanda; Palkóvits, M.; Geenen, Bram; Kos, Aron; Martens, Gerard J.M.; Glennon, Jeffrey; Kaplan, Barry B.; Gaszner, Balázs; Kozicz, Tamás

doi:10.1503/jpn.150154

Cited by 26 publications

(24 citation statements)

References 57 publications

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“…Autophagy is a biological choice for the cells to survive nutrient deprival or harsh environment by recycling degraded cellular compartments . One important finding in the previous study is that miR‐326 was characterized as an upstream regulator of the Ucn1 neuropeptide expression in midbrain neurons, may be associated with regulating cell autophagy . Consistently, our study found that miR‐326 could promote autophagy of dopaminergic neurons in PD, as supported by increased activation of autophagy, expression of LC3‐II, and expression of c‐Jun, and diminished α‐Syn expression in response to miR‐326 mimic.…”

Section: Discussionsupporting

confidence: 85%

MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease

Zhao

Wang

Yang

et al. 2019

J of Cellular Biochemistry

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Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR‐326 in PD through the JNK signaling pathway by targeting X‐box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR‐326 and XBP1 was confirmed. The expression of miR‐326 and XBP1 was measured in PD mice, and gain‐ and loss‐function assay was conducted to examine the regulatory effect of miR‐326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR‐326 mimic and siRNA‐XBP1 showed increased traction test scores, activation of autophagy, expression of LC3‐II, c‐Jun, and p‐α‐Syn, but diminished climbing time and expressions of iNOS, α‐Syn, and p‐c‐Jun. The siRNA‐XBP1 treatment could reverse the effect of miR‐326 inhibitor on PD mice. Overexpression of miR‐326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.

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Section: Discussionsupporting

confidence: 85%

MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease

Zhao

Wang

Yang

et al. 2019

J of Cellular Biochemistry

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“…fMRI studies in humans show that differences in activity of the Edinger-Westphal nucleus correlate with differential responses to sad faces suggesting its involvement in emotional responses, however the resolution of these studies are beyond the ability to recognize the EWcp [104]. Postmortem studies show elevated Ucn1 levels in the EWcp of suicide victims [105]. These few studies indicate that the human EWcp is involved in emotional responses.…”

Section: Limitations and Future Directionsmentioning

confidence: 98%

Involvement of Centrally Projecting Edinger–Westphal Nucleus Neuropeptides in Actions of Addictive Drugs

Zuniga

Ryabinin

2020

Brain Sciences

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The centrally-projecting Edinger–Westphal nucleus (EWcp) is a brain region distinct from the preganglionic Edinger–Westphal nucleus (EWpg). In contrast to the EWpg, the EWcp does not send projections to the ciliary ganglion and appears not to regulate oculomotor function. Instead, evidence is accumulating that the EWcp is extremely sensitive to alcohol and several other drugs of abuse. Studies using surgical, genetic knockout, and shRNA approaches further implicate the EWcp in the regulation of alcohol sensitivity and self-administration. The EWcp is also known as the site of preferential expression of urocortin 1, a peptide of the corticotropin-releasing factor family. However, neuroanatomical data indicate that the EWcp is not a monotypic brain region and consists of several distinct subpopulations of neurons. It is most likely that these subpopulations of the EWcp are differentially involved in the regulation of actions of addictive drugs. This review summarizes and analyzes the current literature of the EWcp’s involvement in actions of drugs of abuse in male and female subjects in light of the accumulating evidence of complexities of this brain region.

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“…Moreover, association of miR-96/182/183 cluster, miR-141/200c cluster, miR-200a/200b/429 cluster [ 41 ], miR-142 and miR-376c [ 42 ], microRNA 381/Hes1 [ 43 ], miR-361-3p [ 44 ], and miR-219 [ 45 ] was linked with the development of hypothalamic abnormalities in various studies. Furthermore, recent studies found that hypothalamic miR-141 [ 46 ], miR-326 [ 47 ], miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, miR-603 [ 48 ], miR-488, miR-144, miR-542-5p, miR-421, miR-376b-5p [ 49 ], miR-543-5p [ 50 ] [ 51 ], and miR-363-3p [ 52 ] are potential contributors in different neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

Mukhopadhyay

Mussa

2020

Brain Sciences

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Background: Neuroinvasion of severe acute respiratory syndrome coronavirus (SARS-CoV) is well documented and, given the similarities between this virus and SARS-CoV-2, it seems that the neurological impairment that is associated with coronavirus disease 2019 (COVID-19) is due to SARS-CoV-2 neuroinvasion. Hypothalamic circuits are exposed to the entry of the virus via the olfactory bulb and interact centrally with crucial respiratory nuclei. Hypothalamic microRNAs are considered as potential biomarkers and modulators for various diseases and future therapeutic targets. The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. Methods: To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. Results: Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. Conclusion: These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.

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MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression

Cited by 26 publications

References 57 publications

MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease

MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease

Involvement of Centrally Projecting Edinger–Westphal Nucleus Neuropeptides in Actions of Addictive Drugs

Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

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