Related Experiment Video
Updated: Jun 14, 2026
08:26
Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
Excitotoxic insults lead to peroxiredoxin hyperoxidation
Frédéric Léveillé1, Francesc X Soriano, Sofia Papadia
1Center for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Oxidative Medicine and Cellular Longevity
|April 2, 2010
Summary
Neuronal antioxidant defenses, regulated by N-methyl-D-aspartate (NMDA) receptor activity, protect against oxidative stress. Both too little and too much NMDA receptor stimulation can lead to peroxiredoxin hyperoxidation, impacting neuronal survival.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Post-mitotic neurons require robust antioxidant defenses for longevity.
- Neuronal antioxidant capacity is modulated by synaptic activity, particularly via N-methyl-D-aspartate (NMDA) receptors.
- The thioredoxin-peroxiredoxin system is a key thiol-based enzymatic pathway for reducing oxidative stress in neurons.
Purpose of the Study:
- To investigate the dose-dependent effect of N-methyl-D-aspartate (NMDA) receptor activity on neuronal peroxiredoxin redox state.
- To elucidate the role of glutamatergic activity levels in neuronal vulnerability to oxidative stress.
- To understand the impact of NMDA receptor stimulation on the thioredoxin-peroxiredoxin system.
Main Methods:
- Electrophysiological recordings to monitor synaptic activity.
- Biochemical assays to assess peroxiredoxin redox state and thioredoxin activity.
- Pharmacological manipulation of NMDA receptor activity in cultured neurons.
Main Results:
- Low levels of NMDA receptor activity increase neuronal sensitivity to peroxiredoxin hyperoxidation.
- Elevated synaptic activity enhances thioredoxin activity and promotes resistance to oxidative stress.
- Excessive glutamate exposure, activating NMDA receptors, acutely induces peroxiredoxin hyperoxidation, demonstrating a U-shaped dose-response curve.
Conclusions:
- NMDA receptor activity critically regulates neuronal antioxidant defense via the thioredoxin-peroxiredoxin system.
- Both insufficient and excessive glutamatergic stimulation can compromise neuronal redox homeostasis.
- Maintaining optimal NMDA receptor activity is essential for preventing peroxiredoxin hyperoxidation and ensuring neuronal survival.
Related Concept Videos
01:27Protein Import into the Peroxisomes
Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
01:24Peroxisomes
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
01:30Peroxisomes
Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within peroxisomes...
01:24Peroxisomes
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
01:16Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:16Cellular Injury IV: Necrosis
Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...