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ORIGINAL RESEARCH ARTICLE

Demystifying the influence of ferroptosis on Alzheimer’s and Parkinson’s diseases: A network and systems biology approach

Deepyaman Das1,2* ,  Chayan Munshi2,3* ,  Kalpesh Jas2,4 ,  Sourish Pramanik2,5
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1 Department of Microbiology, Raiganj University, Raiganj, Uttar Dinajpur, 733134, West Bengal, India
2 Ethophilia (An Autonomous Research Group), Santiniketan, 731235, West Bengal, India
3 Berlin School of Business and Innovation GmbH, Alte Post, Karl-Marx-Straße, 97-99 12043 Berlin, Germany
4 Department of Zoology, Visva Bharati University, Santiniketan, 731235, West Bengal, India
5 Palli Siksha Bhavana, Institute of Agriculture, Visva Bharati University, Sriniketan, 731236, West Bengal, India
Global Translational Medicine 2023, 2(3), 0318 https://doi.org/10.36922/gtm.0318
Submitted: 9 March 2023 | Accepted: 12 July 2023 | Published: 8 August 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Research into the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD) has spanned decades, unraveling deregulated signaling cascades in these diseases. Recently, the discovery of the link between ferroptosis and neurodegeneration has opened new avenues for neurodegenerative disease research. Despite this, the key players in the ferroptotic pathway potentially governing the progression of neurodegenerative disease remain unidentified. Thus, in the present study, we reconstructed two protein–protein interaction networks (PPINs) for AD and PD with their respective differentially expressed genes from post-mortem tissues and identified 21 highly connected clusters within the AD PPIN and 17 clusters within the PD PPIN. Then, we identified 8 ferroptotic transcription factors (FerrTFs) that regulate hub genes from the 7 deregulated clusters of AD and 6 FerrTFs from the 4 deregulated clusters of PD. Functional enrichment analysis of these clusters revealed impairment in important neurological functions. Finally, we identified 681 drugs with potential therapeutic effects against the 8 FerrTFs associated with AD and 633 drugs against the 6 FerrTFs linked to PD. In addition, 126 and 114 miRNAs might silence 7 and 5 FerrTFs against AD and PD, respectively. This exploratory study identifies potential markers of ferroptosis that could exacerbate these neurodegenerative diseases and also suggests possible therapeutic measures against them.

Keywords
Alzheimer’s disease
Parkinson’s disease
Ferroptosis
Transcription factors
Hub genes
Protein–protein interaction network
Funding
None.
Conflict of interest
The authors declare no conflict of interest with any organization or financial entity.
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