Evidence map›Paper›PMID 37542020›Full record

ArticleMolecular diversity2024

Repositioning the existing drugs for neuroinflammation: a fusion of computational approach and biological validation to counter the Parkinson's disease progression.

Harshita Tiwari, Amit Kumar, Manas Ranjan Barik, Harjot Kaur, Shubham Mahajan, Monu Kumar Shukla, Monika Gupta, Govind Yadav, Amit Nargotra

Abstract read
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In one paragraph

Article in Molecular diversity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.4field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Harshita TiwariDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Amit KumarMutagenicity Laboratory, Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India.
Manas Ranjan BarikDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Harjot KaurDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Shubham MahajanDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Monu Kumar ShuklaPK-PD Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Monika GuptaDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Govind YadavMutagenicity Laboratory, Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India.
Amit NargotraDiscovery Informatics, NPMC Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India. anargotra@iiim.res.in.
Indian Institute of Integrative Medicine · INAcademy of Scientific and Innovative Research · IN

Funding

Indian Council of Medical Research 2019-5807
6 · The paper itself

Abstract

Parkinson's disease is caused by the deficiency of striatal dopamine and the accumulation of aggregated α-synuclein in the substantia nigra pars compacta (SNpc). Neuroinflammation associated with oxidative stress is a key factor contributing to the death of dopaminergic neurons in SNpc and advancement of Parkinson's disease. Two molecular targets, i.e., nuclear factor kappa-light-chain-enhancer (NF-kB) and α-synuclein play a substantial role in neuroinflammation progression. Therefore, the compounds targeting these neuroinflammatory targets hold a great potential to combat Parkinson's disease. Thereby, in this study, molecular docking and Connectivity Map (CMap) based gene expression profiling was utilized to reposition the approved drugs as neuroprotective agents for Parkinson's disease. With in silico screening, two drugs namely theophylline and propylthiouracil were selected for anti-neuroinflammatory activity evaluation in in vivo models of chronic neuroinflammation. The neuroinflammatory effect of the identified compounds was confirmed by quantifying the expression of three important neuroinflammatory mediators, i.e. IL-6, TNF-alpha, and IL-1 beta on brain tissue using ELISA assay. The ELISA experiment demonstrated that both compounds significantly decreased the expression of neuroinflammatory mediators, highlighting the compounds' potential in neuroinflammation management. Furthermore, the drug and disease interaction network of the two identified drugs and diseases (neuroinflammation and Parkinson's disease) suggested that the two drugs might interact with various targets namely adenosine receptors, Poly [ADP-ribose] polymerase-1, myeloperoxidase (MPO) and thyroid peroxidase through multiple pathways associated with neuroinflammation and Parkinson's disease. Computational studies suggest that a particular drug may be effective in managing Parkinson's disease associated with neuroinflammation. However, further research is needed to confirm this in biological experiments.

Indexed as

Drug RepositioningMolecular Docking SimulationNeuroprotective AgentsParkinson DiseaseAnimalsAnti-Inflammatory AgentsDisease ProgressionHumansNeuroinflammatory DiseasesTheophyllineAnti-Inflammatory AgentsNeuroprotective AgentsTheophyllineConnectivity map (CMap)ELISAMolecular dockingNetwork analysisNeuroinflammationParkinson’s diseasePropylthiouracilRELASNCATheophylline

Identifiers

PMID37542020
OpenAlexW4385575603

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.