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Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans.
Mol Neurobiol. 2019 Nov; 56(11):7380-7407.MN

Abstract

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.

Authors+Show Affiliations

Neurodegenerative Disease section, Iggy Get Out, 19a Boundary Street, Darlinghurst NSW 2010, Sydney, Australia.Neurodegenerative Disease section, Iggy Get Out, 19a Boundary Street, Darlinghurst NSW 2010, Sydney, Australia.Neurodegenerative Disease section, Iggy Get Out, 19a Boundary Street, Darlinghurst NSW 2010, Sydney, Australia.Neurodegenerative Disease section, Iggy Get Out, 19a Boundary Street, Darlinghurst NSW 2010, Sydney, Australia.Neurodegenerative Disease section, Iggy Get Out, 19a Boundary Street, Darlinghurst NSW 2010, Sydney, Australia. nitin@iggygetout.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31037649

Citation

Brennan, Samuel, et al. "Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans." Molecular Neurobiology, vol. 56, no. 11, 2019, pp. 7380-7407.
Brennan S, Keon M, Liu B, et al. Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans. Mol Neurobiol. 2019;56(11):7380-7407.
Brennan, S., Keon, M., Liu, B., Su, Z., & Saksena, N. K. (2019). Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans. Molecular Neurobiology, 56(11), 7380-7407. https://doi.org/10.1007/s12035-019-1615-1
Brennan S, et al. Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans. Mol Neurobiol. 2019;56(11):7380-7407. PubMed PMID: 31037649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans. AU - Brennan,Samuel, AU - Keon,Matthew, AU - Liu,Bing, AU - Su,Zheng, AU - Saksena,Nitin K, Y1 - 2019/04/29/ PY - 2019/01/06/received PY - 2019/04/15/accepted PY - 2019/5/1/pubmed PY - 2020/3/14/medline PY - 2019/5/1/entrez KW - Biomarker KW - MiRNA KW - Neurodegenerative disease KW - Neuropathology SP - 7380 EP - 7407 JF - Molecular neurobiology JO - Mol Neurobiol VL - 56 IS - 11 N2 - Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/31037649/Panoramic_Visualization_of_Circulating_MicroRNAs_Across_Neurodegenerative_Diseases_in_Humans_ L2 - https://dx.doi.org/10.1007/s12035-019-1615-1 DB - PRIME DP - Unbound Medicine ER -