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Global Translational Medicine

ORIGINAL RESEARCH ARTICLE
Demystifying the influence of ferroptosis on

Alzheimer’s and Parkinson’s diseases: A network
and systems biology approach

2,3
Deepyaman Das *, Chayan Munshi *, Kalpesh Jas , and Sourish Pramanik 2,5
2,4
1,2
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

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
*Corresponding authors:
Deepyaman Das PD with their respective differentially expressed genes from post-mortem tissues and
(deepyaman.das@gmail.com) identified 21 highly connected clusters within the AD PPIN and 17 clusters within the
Chayan Munshi PD PPIN. Then, we identified 8 ferroptotic transcription factors (FerrTFs) that regulate
(chayanbio@gmail.com)
hub genes from the 7 deregulated clusters of AD and 6 FerrTFs from the 4 deregulated
Citation: Das D, Munshi C, clusters of PD. Functional enrichment analysis of these clusters revealed impairment
Jas K, et al., 2023, Demystifying
the influence of ferroptosis on in important neurological functions. Finally, we identified 681 drugs with potential
Alzheimer’s and Parkinson’s therapeutic effects against the 8 FerrTFs associated with AD and 633 drugs against
diseases: A network and systems the 6 FerrTFs linked to PD. In addition, 126 and 114 miRNAs might silence 7 and 5
biology approach. Global Transl
Med, 2(3): 0318. FerrTFs against AD and PD, respectively. This exploratory study identifies potential
https://doi.org/10.36922/gtm.0318 markers of ferroptosis that could exacerbate these neurodegenerative diseases and
also suggests possible therapeutic measures against them.
Received: March 9, 2023
Accepted: July 12, 2023
Published Online: August 8, 2023
Keywords: Alzheimer’s disease; Parkinson’s disease; Ferroptosis; Transcription factors;
Copyright: © 2023 Author(s). Hub genes; Protein–protein interaction network
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. In recent paradigms, ferroptosis has emerged as a key driver of neurological disorders,
Publisher’s Note: AccScience including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The dysregulation of
publishing remains neutral with iron homeostasis is the main cause of ferroptosis, eventually resulting in the progressive
regard to jurisdictional claims in
published maps and institutional loss of neurons in neurodegenerative diseases. This iron-dependent mechanism of
affiliations. ferroptotic cell death is accompanied by the production of highly reactive free radicals

Volume 2 Issue 3 (2023) 1 https://doi.org/10.36922/gtm.0318