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Updated: May 13, 2025
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Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
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A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation
Chiara Bacchella1, Andrea Capucciati1,2, Enrico Monzani1
1Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Antioxidants (Basel, Switzerland)
|April 14, 2025
Summary
Norepinephrine (NE) has dual roles in neurodegenerative diseases like Alzheimer's and Parkinson's. Its oxidation can lead to toxic protein aggregation and neuromelanin (NM) formation, highlighting the need for homeostatic balance.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Neurodegenerative disorders pose a significant global health challenge.
- Understanding the molecular etiology of Alzheimer's and Parkinson's diseases is crucial.
- Norepinephrine (NE) and its associated pathways are implicated in these disorders.
Purpose of the Study:
- To review the dual beneficial and toxic effects of norepinephrine (NE).
- To elucidate the role of ROS/metal-mediated pathways in neuromelanin (NM) formation and protein aggregation.
- To highlight the importance of maintaining homeostatic balance in catecholamine oxidation and neuroprotein modification.
Main Methods:
- Literature review of current research on norepinephrine, oxidative stress, and neurodegeneration.
- Analysis of molecular mechanisms involving ROS, metal ions, and catecholamine oxidation.
- Examination of pathways leading to neuroprotein modification, aggregation, and neuromelanin organelle formation.
Main Results:
- Norepinephrine (NE) exhibits both beneficial and toxic effects.
- ROS/metal-mediated pathways contribute to NE oxidation, generating by-products.
- These by-products can modify neuroproteins, leading to altered stability, oligomerization, and incorporation into neuromelanin (NM) organelles.
Conclusions:
- Stabilizing the homeostatic balance is critical to prevent detrimental NE oxidation.
- Dysregulation of these pathways can promote protein aggregation and neurodegeneration.
- Further research is needed to address challenges and controversies in the field.
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