Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases

Konovalova, Julia; Gerasymchuk, Dmytro; Parkkinen, Ilmari; Chmielarz, Piotr; Domanskyi, Andrii

doi:10.3390/ijms20236055

Cited by 150 publications

(133 citation statements)

References 226 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…It has previously been linked to PD in cell culture models, assessing environmental neurotoxicant mangane, in which miR210 was identified in EVs [147]. The interplay between oxidative stress and microRNAs has been shown in a number of neurodegenerative diseases including AD, PD, HD, and ALS [148]. Oxidative stress has indeed been suggested to play key roles in PD, although some parameters from clinical studies have been inconsistent [149].…”

Section: Discussionmentioning

confidence: 99%

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

Sancandi¹,

Uysal-Onganer

Kraev

et al. 2020

IJMS

View full text Add to dashboard Cite

The identification of biomarkers for early diagnosis of Parkinson's disease (PD) is of pivotal importance for improving approaches for clinical intervention. The use of translatable animal models of pre-motor PD therefore offers optimal opportunities for novel biomarker discovery in vivo. Peptidylarginine deiminases (PADs) are a family of calcium-activated enzymes that contribute to protein misfolding through post-translational deimination of arginine to citrulline. Furthermore, PADs are an active regulator of extracellular vesicle (EV) release. Both protein deimination and extracellular vesicles (EVs) are gaining increased attention in relation to neurodegenerative diseases, including in PD, while roles in pre-motor PD have yet to be investigated. The current study aimed at identifying protein candidates of deimination in plasma and plasma-EVs in a rat model of pre-motor PD, to assess putative contributions of such post-translational changes in the early stages of disease. EV-cargo was further assessed for deiminated proteins as well as three key micro-RNAs known to contribute to inflammation and hypoxia (miR21, miR155, and miR210) and also associated with PD. Overall, there was a significant increase in circulating plasma EVs in the PD model compared with sham animals and inflammatory and hypoxia related microRNAs were significantly increased in plasma-EVs of the pre-motor PD model. A significantly higher number of protein candidates were deiminated in the pre-motor PD model plasma and plasma-EVs, compared with those in the sham animals. KEGG (Kyoto encyclopedia of genes and genomes) pathways identified for deiminated proteins in the pre-motor PD model were linked to "Alzheimer's disease", "PD", "Huntington's disease", "prion diseases", as well as for "oxidative phosphorylation", "thermogenesis", "metabolic pathways", "Staphylococcus aureus infection", gap junction, "platelet activation", "apelin signalling", "retrograde endocannabinoid signalling", "systemic lupus erythematosus", and "non-alcoholic fatty liver disease". Furthermore, PD brains showed significantly increased staining for total deiminated proteins in the brain vasculature in cortex and hippocampus, as well as increased immunodetection of deiminated histone H3 in dentate gyrus and cortex. Our findings identify EVs and post-translational protein deimination as novel biomarkers in early pre-motor stages of PD. Figure 2. EV characterisation from rat plasma. (A) Representative Nanosight graphs showing nanoparticle tracking analysis (NTA) analysis of plasma EV profiles from sham-treated rats (Sham; n = 3). (B) Representative Nanosight graphs showing NTA analysis of plasma EV profiles from the premotor PD rat models (PD; n = 3). (C) Western blotting (WB) confirms that rat plasma-EVs are positive for the EV-specific markers CD63 and flotillin-1 (Flot-1); the molecular weight standard is indicated in kilo Daltons (kDa). (D,E) Transmission electron microscopy (TEM) images showing EVs isolated from sham (D) and pre-motor PD model (PD; (E)) rat plasma, revea...

show abstract

Section: Discussionmentioning

confidence: 99%

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

Sancandi¹,

Uysal-Onganer

Kraev

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…MiRNAs have shown to be abnormal in various regions of the brains of HD patients [66]. Previous study used the postmortem brains of HD patients to show that miR-22 has protective mechanisms against the disease [67].…”

Section: Bdnf Associated Micrornas In Huntington's Diseasementioning

confidence: 99%

The Relation of the Brain-Derived Neurotrophic Factor with MicroRNAs in Neurodegenerative Diseases and Ischemic Stroke

et al. 2020

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that plays a crucial role in the development of the nervous system while supporting the survival of existing neurons and instigating neurogenesis. Altered levels of BDNF, both in the circulation and in the central nervous system (CNS), have been reported to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), multiple sclerosis (MS), and ischemic stroke. MicroRNAs (miRNAs) are a class of non-coding RNAs found in body fluids such as peripheral blood and cerebrospinal fluid. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of neurodegenerative and neurovascular diseases. Thus, they present as promising biomarkers and a novel treatment approach for CNS disorders. Currently, limited studies provide viable evidence of miRNA-mediated post-transcriptional regulation of BDNF. The aim of this review is to provide a comprehensive assessment of the current knowledge regarding the potential diagnostic and prognostic values of miRNAs affecting BDNF expression and its role as a CNS disorders and neurovascular disease biomarker. Moreover, a novel therapeutic approach in neurodegenerative diseases and ischemic stroke targeting miRNAs associated with BDNF will be discussed.

show abstract

“…miRNAs are gaining more and more attention as a mechanism to regulate gene expression. Abnormal levels of different miRNAs were found in different neurodegenerative disorders, including but not limited to AD [ 2 , 23 , 41 ], where they regulate pathways including axonal guidance, apoptosis, oxidative stress, and inflammation, indicating that these pathways are commonly altered features in neurodegeneration [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Modulate the Pathogenesis of Alzheimer’s Disease: An In Silico Analysis in the Human Brain

Chiricosta

Boccardi

Mecocci

et al. 2020

Genes

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small RNAs involved in the post-transcriptional regulation of their target genes, causing a decrease in protein translation from the mRNA. Different miRNAs are found in the nervous system, where they are involved in its physiological functions, but altered miRNAs expression was also reported in neurodegenerative disorders, including Alzheimer’s disease (AD). AD is characterized by memory loss, cognitive function abnormalities, and various neuropsychiatric disturbances. AD hallmarks are amyloid β (Aβ) aggregates, called senile plaques, and neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein. In this study, we performed an in silico analysis to evaluate altered patterns of miRNAs expression in the brains of AD patients compared to healthy subjects. We found 12 miRNAs that were differentially expressed in AD compared to healthy individuals. These miRNAs have target genes involved in AD pathogenesis. In particular, some miRNAs influence Aβ production, having as target secretase and amyloid precursor protein (APP). Some miRNAs were reported to be involved in nervous system functions, and their alteration can cause neuronal dysfunction.

show abstract

Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases

Cited by 150 publications

References 226 publications

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

The Relation of the Brain-Derived Neurotrophic Factor with MicroRNAs in Neurodegenerative Diseases and Ischemic Stroke

MicroRNAs Modulate the Pathogenesis of Alzheimer’s Disease: An In Silico Analysis in the Human Brain

Contact Info

Product

Resources

About