Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans.

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans.

Publication date: Apr 29, 2019

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.

Brennan, S., Keon, M., Liu, B., Su, Z., and Saksena, N.K. Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans. 17852. 2019 Mol Neurobiol.

Concepts Keywords
ALS Genomic proteomic technologies
Alzheimer MicroRNA
Amyotrophic Lateral Sclerosis Gene expression
Bioinformatic RNA
Biomarkers Final resolution diseases
Cognate Genomic proteomic technologies
Convergence
Dementia
ECM
Fatty Acid Synthesis
Final Resolution
Metabolism
MicroRNA
MicroRNAs
Multiple Sclerosis
NDS
NDs
Neurodegenerative
Neurodegenerative Diseases
Neuron
Parkinson
Prion
Proteomic
Receptor
Throughput

Semantics

Type Source Name
disease DOID Neurodegenerative disease
disease MESH development
pathway BSID Prion diseases
disease MESH prion diseases
gene UNIPROT MMRN1
pathway BSID Metabolism
gene UNIPROT MLXIP
gene UNIPROT MYLIP
gene UNIPROT MARCH8
gene UNIPROT ALB
disease DOID dementia
disease MESH dementia
gene UNIPROT SOD1
gene UNIPROT IGFALS
disease DOID amyotrophic lateral sclerosis
disease MESH amyotrophic lateral sclerosis
disease DOID multiple sclerosis
disease MESH multiple sclerosis
pathway BSID Neurodegenerative Diseases
disease MESH Neurodegenerative Diseases

Original Article

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