Raj G, Kumar M, Shreya S, Bhardwaj S, Priya R, Mangalhara KC, Jain BP. Dithiothreitol induced endoplasmic reticulum stress and its role in neurodegeneration in Caenorhabditis elegans. World J Biol Chem 2025; 16(4): 111110 [DOI: 10.4331/wjbc.v16.i4.111110]
Corresponding Author of This Article
Buddhi Prakash Jain, Assistant Professor, Gene Expression and Signaling Lab, Department of Zoology, Mahatma Gandhi Central University, Mgcub Motihari, Motihari 845401, Bihar, India. buddhiprakash@mgcub.ac.in
Research Domain of This Article
Neurosciences
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Govind Raj, Manish Kumar, Smriti Shreya, Shikha Bhardwaj, Ratna Priya, Department of Zoology, Mahatma Gandhi Central University, Motihari 845401, India
Kailash C Mangalhara, Department of Oncology, Salk Institute for Biological Studies, La Jolla, San Diego, CA 92037, United States
Buddhi Prakash Jain, Gene Expression and Signaling Lab., Department of Zoology, Mahatma Gandhi Central University, Motihari 845401, Bihar, India
Author contributions: Jain BP conceptualized the idea, finally edited the finalized the manuscript; Jain BP and Raj G wrote the manuscript; Raj G performed majority of the experiments; Kumar M and Priya R helped in the experimentation part on C. elegans; Shreya S and Bhardwaj S performed western blotting experiment; Mangalhara KC helped in the editing and revising the manuscript; Jain BP and Priya R performed the revision of the manuscript.
Institutional review board statement: In the present work, no approval from institutional review board is required as the research work was carried out on C. elegans model system.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: Data will be shared upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Buddhi Prakash Jain, Assistant Professor, Gene Expression and Signaling Lab, Department of Zoology, Mahatma Gandhi Central University, Mgcub Motihari, Motihari 845401, Bihar, India. buddhiprakash@mgcub.ac.in
Received: June 26, 2025 Revised: July 16, 2025 Accepted: October 27, 2025 Published online: December 5, 2025 Processing time: 164 Days and 1.8 Hours
Abstract
BACKGROUND
Neurodegeneration refers to the progressive loss of neurons, affecting both their structure and function. It is driven by synaptic dysfunction, disruptions in neural networks, and the accumulation of abnormal protein variants. Endoplasmic reticulum (ER) stress, caused by the accumulation of misfolded or unfolded protein, is a major contributor to neurodegeneration. Dithiothreitol (DTT) is a widely used redox reagent that disrupts the oxidative protein folding environment, inducing ER stress and leading to the imbalance in protein homeostasis can activate stress response pathway, potentially contributing to neurodegenerative processes. Caenorhabditis elegans (C. elegans) is a widely used model organism for studying neurodegeneration due to its well-mapped nervous system, approximately one-third of neuron cells in their body, complete genome sequenced, and conserved stress response pathway.
AIM
To study the neurodegeneration in C. elegans caused by DTT-induced ER stress, assessed by behavioral, molecular, and lifespan changes.
METHODS
C. elegans were cultured on nematode growth medium plates with OP50, and ER stress was induced using DTT. Effects were assessed via behavioral assays such as locomotion, chemotaxis, lifespan assay, and molecular studies.
RESULTS
DTT exposure led to a significant decline in locomotion and chemotaxis response, indicating neurotoxicity. A reduction in lifespan was observed, suggesting an overall impact on health. Molecular analysis confirmed ER stress activation. DTT-induced ER stress negatively affects C. elegans, leading to behavioral impairments and molecular alterations associated with neurodegeneration.
CONCLUSION
These findings establish C. elegans as a potential model for studying ER stress-mediated neurotoxicity and its implications in neurodegenerative diseases.
Core Tip: Disturbancein the Protein folding process induces Endoplasmic Reticulum Stress and sueseqeunct activation of unfolded Protein Response. accumulation of misfolded or unfolded proteins has been reported in the pathogenesis of several neurodegenerative diseases. Dithiothreitol (DTT), a potent endoplasmic reticulum stress inducer might involve in neurodegenration and related disorders. The present work aims to study the effects of DTT on the unfolded protein response activation and neurobehavioural effects in the Caenorhabditis elegans.
