MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration

Xiong, Ran; Wang, Zhiquan; Zhao, Zongbo; Li, Hui; Chen, Wei; Zhang, Bei; Wang, Liling; Wu, Langping; Li, Wen; Ding, Jianqing; Chen, Shengdi

doi:10.1016/j.neurobiolaging.2013.09.027

Cited by 94 publications

(61 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Natalizumab and Glatiramer Acetate treatments have also been reported to alter MS patient miRNA expression (Waschbisch et al, 2011; Sievers et al, 2012); it will be important, in future studies, to address Dicer expression levels and activity in these and other treatments. These miRNAs’ expression and responses to treatment should also be evaluated in other neurological and autoimmune diseases especially in view of several studies that have implicated miR-125 in inflammatory weakening of the blood brain barrier and miR-494 as a key regulator in Parkinson’s Disease (Le et al, 2009; Lattanzi et al, 2013; Reijerkerk et al, 2013; Stappert et al, 2013; Xiong et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

“…Xiong et al (Xiong et al, 2014) showed that miR-494 is elevated in Parkinson’s Disease and identified DJ-1, a putative sensor of oxidative stress, as its target. Elevated miR-494 reduced DJ-1 expression and exacerbated neurodegeneration in dopaminergic neurons (Xiong et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated miR-494 reduced DJ-1 expression and exacerbated neurodegeneration in dopaminergic neurons (Xiong et al, 2014). We found that miR-494 is elevated in RRMS and further elevated in SPMS but was restored to healthy control levels in patients responding well to IFNβ1a (Figure 4C).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Dicer and microRNA expression in multiple sclerosis and response to interferon therapy

Magner

Weinstock‐Guttman

Rho

et al. 2016

Journal of Neuroimmunology

View full text Add to dashboard Cite

Dysregulation of microRNA expression has been shown in multiple sclerosis (MS); however, the mechanisms underlying these changes, their response to therapy and the impact of microRNA changes in MS are not completely understood. Dicer mediates the cleavage of precursor microRNAs to mature microRNAs and is dysregulated in multiple pathologies. Having shown that interferons regulate Dicer in vitro, we hypothesized that MS patient IFNβ1a treatment could potentially alter Dicer expression. Dicer mRNA and protein levels, as well as microRNA expression, were determined in MS patient and healthy control PBL. Acute responses to IFNβ1a were assessed in 50 patients. We found that Dicer protein but not mRNA levels decrease in MS patients while both are selectively induced in patients responding well to IFNβ1a. Potential microRNA biomarkers for relapsing remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS) and IFNβ1a response are described. Contrasts in Dicer and microRNA expression levels between patient populations may offer insight into mechanisms underlying disease courses and responses to IFNβ1a therapy. This work identifies Dicer regulation as both a potential mediator of MS pathology and a therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dicer and microRNA expression in multiple sclerosis and response to interferon therapy

Magner

Weinstock‐Guttman

Rho

et al. 2016

Journal of Neuroimmunology

View full text Add to dashboard Cite

show abstract

“…De -stabilizing mutations in DJ-1 result in familial PD, and diminished protein content of DJ-1 has been reported in sporadic cases of PD [ 10, 11]. Furthermore, knockout or knockdown of DJ-1 results in increased susceptibility to toxin-induced dopaminergic cell death in vivo [37, 38]. These studies indicate that protein levels of DJ-1 play an important role in protecting against dopaminergic degeneration.…”

Section: Discussionmentioning

confidence: 99%

Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson’s Disease

et al. 2016

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glutathionylation is a prevalent redox modification of proteins resulting from the disulfide adduction of the glutathione moiety to a reactive cysteine-SH; and glutathionylation of specific proteins has been implicated in regulation of cell viability. Glutaredoxin 1 (Grx1) is the principal deglutathionylating enzyme within cells, and it has been reported to mediate protection of dopaminergic neurons in C. elegans, however many of the functional downstream targets of Grx1 in vivo remain unknown. Previously, DJ-1 protein content was shown to decrease concomitantly with diminution of Grx1 protein content in cell culture of model neurons (SH-SY5Y and Neuro-2A lines). In the current study we aimed to investigate the regulation of DJ-1 by Grx1 in vivo and characterize its glutathionylation in vitro. Here, with Grx−/− mice we provide evidence that Grx1 regulates protein levels of DJ-1 in vivo. Furthermore, with model neuronal cells (SH-SY5Y) we observed decreased DJ-1 protein content in response to treatment with known glutathionylating agents; and with isolated DJ-1 we identified two distinct sites of glutathionylation. Finally, we found that overexpression of DJ-1 in the dopaminergic neurons partly compensates for the loss of the Grx1 homolog in a C. elegans in vivo model of PD. Therefore; our results reveal a novel redox modification of DJ-1 and suggest a novel regulatory mechanism for DJ-1 content in vivo.

show abstract

“…The identification of DJ-1, a stabilizer of Nrf2, as a direct target of miR-494 is fundamental in this context [167]. While the overexpression of this miR renders neuroblastoma N2a cells more susceptible to oxidative stress and exacerbates neurodegeneration in MPTP treated mice [162], its reduction might protect neurons against oxidative insult by increasing SOD1 expression, as well as by attenuating mitochondrial dysfunctions [168].…”

Section: Nrf2 and Mirnas In Parkinson's Diseasementioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

show abstract

MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration

Cited by 94 publications

References 34 publications

Dicer and microRNA expression in multiple sclerosis and response to interferon therapy

Dicer and microRNA expression in multiple sclerosis and response to interferon therapy

Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson’s Disease

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Contact Info

Product

Resources

About