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Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Differential Expression of MicroRNAs and Predicted Drug Target in Amyotrophic Lateral Sclerosis
Riya Ben Patel1, Akhilesh Kumar Bajpai2, Kavitha Thirumurugan3
1#412J, Structural Biology Lab, Pearl Research Park, School of Biosciences & Technology, Vellore Institute of Technology, Vellore-632014, India.
Abstract:
ALS (Amyotrophic Lateral Sclerosis) is a rare type of neurodegenerative disease. It shows progressive degradation of motor neurons in the brain and spinal cord. At present, there is no treatment available that can completely cure ALS. The available treatments can only increase a patient's life span by a few months. Recently, microRNAs (miRNAs), a sub-class of small non-coding RNAs have been shown to play an essential role in the diagnosis, prognosis, and therapy of ALS. Our study focuses on analyzing differential miRNA profiles and predicting drug targets in ALS using bioinformatics and computational approach. The study identifies eight highly differentially expressed miRNAs in ALS patients, four of which are novel. We identified 42 hub genes for these eight highly expressed miRNAs with Amyloid Precursor Protein (APP) as a candidate gene among them for highly expressed down-regulated miRNA, hsa-miR-455-3p using protein-protein interaction network and Cytoscape analysis. A novel association has been found between hsa-miR-455-3p/APP/serotonergic pathway using KEGG pathway analysis. Also, molecular docking studies have revealed curcumin as a potential drug target that may be used for the treatment of ALS. Thus, the present study has identified four novel miRNA biomarkers: hsa-miR-3613-5p, hsa-miR-24, hsa-miR-3064-5p, and hsa-miR-4455. There is a formation of a novel axis, hsa-miR-455-3p/APP/serotonergic pathway, and curcumin is predicted as a potential drug target for ALS.
Insights
This study identifies novel microRNA biomarkers for Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease. Curcumin shows potential as a therapeutic drug target for ALS treatment.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with no cure.
- Current treatments offer limited lifespan extension.
- MicroRNAs (miRNAs) are implicated in ALS diagnosis, prognosis, and therapy.
Purpose of the Study:
- To analyze differential miRNA profiles in ALS patients.
- To predict potential drug targets for ALS using bioinformatics.
- To identify novel miRNA biomarkers and therapeutic strategies for ALS.
Main Methods:
- Bioinformatics and computational approaches were employed.
- Differential miRNA expression analysis was performed.
- Protein-protein interaction networks, Cytoscape, KEGG pathway analysis, and molecular docking were utilized.
Main Results:
- Eight highly differentially expressed miRNAs were identified in ALS patients, including four novel ones.
- A novel axis, hsa-miR-455-3p/Amyloid Precursor Protein (APP)/serotonergic pathway, was identified.
- Curcumin was predicted as a potential drug target for ALS via molecular docking.
Conclusions:
- Four novel miRNA biomarkers (hsa-miR-3613-5p, hsa-miR-24, hsa-miR-3064-5p, hsa-miR-4455) for ALS were identified.
- The study established a new hsa-miR-455-3p/APP/serotonergic pathway association.
- Curcumin presents a promising therapeutic candidate for ALS treatment.

