MicroRNA-4639 is a regulator of DJ-1 expression and a potential diagnostic marker for early Parkinson’s disease

Chen, Yuanchang; Ding, Jing; Chen, S.

doi:10.1016/j.parkreldis.2017.11.078

Cited by 20 publications

(28 citation statements)

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“…Different miRNA profiles are found in PD and other neurodegenerative disorders, with increased expression of miR-30a-5p, miR-153, and miR-4639-5p being identified in PD compared with unaffected healthy individuals. [232][233][234] Thus, it is likely that, in the near future, the application of miRNA panels on body-fluids such as a serum, saliva, and cerebrospinal fluid may provide potential PD diagnostic biomarkers, and may also help stratify PD patients according to the genetic and molecular pathways involved.…”

Section: Mirna Therapeuticsmentioning

confidence: 99%

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

Mastaglia

Fletcher

et al. 2020

Medicinal Research Reviews

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Parkinson's disease (PD) is one of the most common neurodegenerative disorders that manifest various motor and nonmotor symptoms. Although currently available therapies can alleviate some of the symptoms, the disease continues to progress, leading eventually to severe motor and cognitive decline and reduced life expectancy. The past two decades have witnessed rapid progress in our understanding of the molecular and genetic pathogenesis of the disease, paving the way for the development of new therapeutic approaches to arrest or delay the neurodegenerative process. As a result of these advances, biomarker-driven subtyping is making it possible to stratify PD patients into more homogeneous subgroups that may better respond to potential genetic-molecular pathway targeted disease-modifying therapies. Therapeutic nucleic acid oligomers can bind to target gene sequences with very high specificity in a base-pairing manner and precisely modulate downstream molecular events. Recently, nucleic acid therapeutics have proven effective in the treatment of a number of severe neurological and neuromuscular disorders, drawing increasing attention to the possibility of developing novel molecular therapies for PD. In this

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Section: Mirna Therapeuticsmentioning

confidence: 99%

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

Mastaglia

Fletcher

et al. 2020

Medicinal Research Reviews

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“…Accordingly, the depletion of these miRNAs directly contributes for decreased levels of DJ-1 in brains from PD, with a direct binding to the 3′-untranslated region (3′-UTR) of their mRNAs which proves their neuroprotective role [46]. Additionally, miR-4639 and miR-494 were identified in the list of potential inhibitors of DJ-1 expression, suggesting the measurement of their levels in human plasma as prognostic biomarkers of PD [48,49] (Figure 1). Similarly to the effects of miR-34 b/c, it was confirmed that miR-7 also plays a key role in α-Syn repression by directly binding to the 3′-UTR sequence of its mRNA in different experimental models such as SH-SY5Y cells, HEK293T cells, primary neurons, and pancreatic islets [50][51][52].…”

Section: Regulation Of α-Synuclein Expressionmentioning

confidence: 99%

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Dimitrova-Shumkovska¹,

Krstanoski²

2020

Synucleins - Biochemistry and Role in Diseases

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The molecular responses to counteract diseases, including insulting conditions such as injury and pathogen infection, involve coordinated modulation of gene expression programs. The association of alpha synuclein (α-Syn) with several progressive disorders has focused the research on its induced conformational behavior as critical for uncovering the "secrets" for progression of α-synucleinopathies. Cholesterol is one of the lipid components crucial for regular proliferation of the nervous tissue. Its interaction with α-Syn may offer other insights to α-Syn normal expression. Discovering that the molecular regulatory mechanisms responsible for prevention of α-Syn aggregation may be manifested through microRNA (miRNA) regulated gene expression is also crucial for widening the perception of neuropathology. The 18-kDa translocator protein (TSPO) localized on the outer mitochondrial membrane is able to regulate various cellular and tissue functions, with key role as cholesterol transporter for neurosteroid synthesis. TSPO up-regulation, has been connected to several diseases, including cancer, neuronal damage, and inflammation. Connection may also be established between TSPO expression and fatty acid oxidation, thus unveiling new possibilities in the research of α-Syn overexpression. However, expression of TSPO in the neuroinflammatory environment is probably the best starting point for targeting TSPO as a suitable therapeutic target.

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“…Furthermore, FARNA suggests that hsa-miR-4639 is implicated in heart failure. On the other hand, Chen et al demonstrated that increased levels of hsa-miR-4639 in plasma leads to downregulation of the DJ-1 protein activity in patients with Parkinson's disease [138]. Moreover, they demonstrated that miR-4639-5p directly binds the DJ-1 transcript at its 3 ′ UTR that results in the downregulation of the DJ-1 protein activity.…”

Section: Example 2: Hypotheses and Potentially New Insightsmentioning

confidence: 99%

Literature-Based Enrichment Insights into Redox Control of Vascular Biology

Essack

Salhi

Stanimirović

et al. 2019

Oxidative Medicine and Cellular Longevity

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In cellular physiology and signaling, reactive oxygen species (ROS) play one of the most critical roles. ROS overproduction leads to cellular oxidative stress. This may lead to an irrecoverable imbalance of redox (oxidation-reduction reaction) function that deregulates redox homeostasis, which itself could lead to several diseases including neurodegenerative disease, cardiovascular disease, and cancers. In this study, we focus on the redox effects related to vascular systems in mammals. To support research in this domain, we developed an online knowledge base, DES-RedoxVasc, which enables exploration of information contained in the biomedical scientific literature. The DES-RedoxVasc system analyzed 233399 documents consisting of PubMed abstracts and PubMed Central full-text articles related to different aspects of redox biology in vascular systems. It allows researchers to explore enriched concepts from 28 curated thematic dictionaries, as well as literature-derived potential associations of pairs of such enriched concepts, where associations themselves are statistically enriched. For example, the system allows exploration of associations of pathways, diseases, mutations, genes/proteins, miRNAs, long ncRNAs, toxins, drugs, biological processes, molecular functions, etc. that allow for insights about different aspects of redox effects and control of processes related to the vascular system. Moreover, we deliver case studies about some existing or possibly novel knowledge regarding redox of vascular biology demonstrating the usefulness of DES-RedoxVasc. DES-RedoxVasc is the first compiled knowledge base using text mining for the exploration of this topic.

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MicroRNA-4639 is a regulator of DJ-1 expression and a potential diagnostic marker for early Parkinson’s disease

Cited by 20 publications

References 0 publications

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Literature-Based Enrichment Insights into Redox Control of Vascular Biology

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