Alterations of miRNAs reveal a dysregulated molecular regulatory network in Parkinson’s disease striatum

Nair, Venugopalan D.; Ge, Yongchao

doi:10.1016/j.neulet.2016.06.061

Cited by 55 publications

(37 citation statements)

References 39 publications

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“…We have found multiple associations with PD (and other motor disorders) through ion channel deficiencies (Mourre et al, 2017 ; Roeper, 2017 ), miRNAs (Tan et al, 2013 ; Nair and Ge, 2016 ), epigenetic alterations (Coppedè, 2012 ) and alterations in MHC-I (Cebrian et al, 2014 ); some of them associating the same cerebral structures like the ones we have found. Our results are particularly interesting given that some of the latter hypothesis of PD etiology has previously involved the microbiota as a relevant and mechanistic factor (Parashar and Udayabanu, 2017 ).…”

Section: Discussionsupporting

confidence: 63%

“…These are known to have a role in neuropsychiatric disorders (Alural et al, 2017 ), anxiety-like behaviors (Hoban et al, 2017b ) and movement disorders (Tan et al, 2013 ). Increased miRNAs have been reported in GF–mice at amygdala and prefrontal cortex (Hoban et al, 2017a ) and in the striatum (putamen and caudate) (Diaz Heijtz et al, 2011 ) as well as in post-mortem humans with PD compared to healthy controls (Nair and Ge, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

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An Ontology Systems Approach on Human Brain Expression and Metaproteomics

2018

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Research in the last decade has shown growing evidence of the gut microbiota influence on brain physiology. While many mechanisms of this influence have been proposed in animal models, most studies in humans are the result of a pathology–dysbiosis association and very few have related the presence of certain taxa with brain substructures or molecular pathways. In this paper, we associated the functional ontologies in the differential expression of brain substructures from the Allen Brain Atlas database, with those of the metaproteome from the Human Microbiome Project. Our results showed several coherent clustered ontologies where many taxa could influence brain expression and physiology. A detailed analysis of psychobiotics showed specific slim ontologies functionally associated with substructures in the basal ganglia and cerebellar cortex. Some of the most relevant slim ontology groups are related to Ion transport, Membrane potential, Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant neuropathology found was Parkinson disease. In some of these cases, new hypothetical gut microbiota-brain interaction pathways are proposed.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

An Ontology Systems Approach on Human Brain Expression and Metaproteomics

2018

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“…MiRNAs expression typically vary depending on the progression of PD and the specific stage of the disease, resulting in the heterogeneity of the miRNAs. The dysfunction of these miRNAs can result in a series of problems, including downregulation of DJ-1 protein (Xiong et al, 2014 ; Zhang and Cheng, 2014 ), overexpression of α-synuclein (Zhang and Cheng, 2014 ), upregulation of pathogenic LRRK2 protein (Rassu et al, 2017 ), up- or down-regulation of inflammatory response (Nair and Ge, 2016 ; Zhou et al, 2016 ), dysregulation of the IGF (Kim et al, 2014 ), and even the death of dopaminergic neuronal (Chmielarz et al, 2017 ). Since circulating miRNAs are supposed to be tissue-specific, abundant, highly stable and quantifiable and they are up- or down-regulated several years before the onset of PD, a novel approach to using miRNAs as non-invasive biomarkers to detect the early PD and monitor the progression of the pathology has been proposed.…”

Section: Biochemical Biomarkersmentioning

confidence: 99%

Recent Advances in Biomarkers for Parkinson’s Disease

Yan

Guo

et al. 2018

Front. Aging Neurosci.

144

128

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Parkinson’s disease (PD) is one of the common progressive neurodegenerative disorders with several motor and non-motor symptoms. Most of the motor symptoms may appear at a late stage where most of the dopaminergic neurons have been already damaged. In order to provide better clinical intervention and treatment at the onset of disease, it is imperative to find accurate biomarkers for early diagnosis, including prodromal diagnosis and preclinical diagnosis. At the same time, these reliable biomarkers can also be utilized to monitor the progress of the disease. In this review article, we will discuss recent advances in the development of PD biomarkers from different aspects, including clinical, biochemical, neuroimaging and genetic aspects. Although various biomarkers for PD have been developed so far, their specificity and sensitivity are not ideal when applied individually. So, the combination of multimodal biomarkers will greatly improve the diagnostic accuracy and facilitate the implementation of personalized medicine.

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“…This aspect appears of specific interest in light of the study of Nair and collaborators, showing that the differentially expressed miRNAs found in post-mortem PD-striatum were associated to the inflammatory response. In particular, using a pathway predictive analysis tool, the authors found that the majority of the predicted altered transcripts (as a consequence of miRNA dysregulation), were significantly associated with NF-κB pro-inflammatory network, in turn linked with neuronal signaling and stress response (see also Section 4 ) [ 116 ]. Altogether these studies may lead to the identification of new druggable targets for downregulating microglial activation and possibly mitigate DAergic neuron death in PD (see also Section 6 ).…”

Section: Regulation Of Pd-related Genes Mediated By Mirnasmentioning

confidence: 99%

“…Computational analysis showed that many of these miRNAs were associated with inflammatory response and other mechanisms activated by oxidative stress in PD striatum. Considering that almost all PD patients in this study were treated with L-DOPA, the authors suggested that miRNAs found dysregulated in PD, might mediate antioxidant effect of the drug treatment, by suppressing proinflammatory factors and upregulating antioxidant factors [ 116 ].…”

Section: Mirnas In Post-mortem Pd Brain-derived Samplesmentioning

confidence: 99%

microRNAs in Parkinson’s Disease: From Pathogenesis to Novel Diagnostic and Therapeutic Approaches

Leggio

Vivarelli

L’Episcopo

et al. 2017

IJMS

194

136

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Parkinson’s disease (PD) is the most prevalent central nervous system (CNS) movement disorder and the second most common neurodegenerative disease overall. PD is characterized by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) within the midbrain, accumulation of alpha-synuclein (α-SYN) in Lewy bodies and neurites and excessive neuroinflammation. The neurodegenerative processes typically begin decades before the appearance of clinical symptoms. Therefore, the diagnosis is achievable only when the majority of the relevant DAergic neurons have already died and for that reason available treatments are only palliative at best. The causes and mechanism(s) of this devastating disease are ill-defined but complex interactions between genetic susceptibility and environmental factors are considered major contributors to the etiology of PD. In addition to the role of classical gene mutations in PD, the importance of regulatory elements modulating gene expression has been increasingly recognized. One example is the critical role played by microRNAs (miRNAs) in the development and homeostasis of distinct populations of neurons within the CNS and, in particular, in the context of PD. Recent reports demonstrate how distinct miRNAs are involved in the regulation of PD genes, whereas profiling approaches are unveiling variations in the abundance of certain miRNAs possibly relevant either to the onset or to the progression of the disease. In this review, we provide an overview of the miRNAs recently found to be implicated in PD etiology, with particular focus on their potential relevance as PD biomarkers, as well as their possible use in PD targeted therapy.

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Alterations of miRNAs reveal a dysregulated molecular regulatory network in Parkinson’s disease striatum

Cited by 55 publications

References 39 publications

An Ontology Systems Approach on Human Brain Expression and Metaproteomics

An Ontology Systems Approach on Human Brain Expression and Metaproteomics

Recent Advances in Biomarkers for Parkinson’s Disease

microRNAs in Parkinson’s Disease: From Pathogenesis to Novel Diagnostic and Therapeutic Approaches

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