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Dithiothreitol induced endoplasmic reticulum stress and its role in neurodegeneration in Caenorhabditis elegans

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摘要 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 onethird 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.
出处 《World Journal of Biological Chemistry》 2025年第4期75-86,共12页 世界生物化学杂志(英文)
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