Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis
Abstract
Oxidative stress occurs in a variety of disease settings and is strongly linked to the development of neuron death and neuronal dysfunction. Cells are equipped with numerous pathways to prevent the genesis, as well as the consequences, of oxidative stress in the brain. In this review we discuss the various forms and sources of oxidative stress in the brain and briefly discuss some of the complexities in detecting the presence of oxidative stress. We then focus the review on the interplay between the diverse cellular proteolytic pathways and their roles in regulating oxidative stress in the brain. Additionally, we discuss the involvement of protein synthesis in regulating the downstream effects of oxidative stress. Together, these components of the review demonstrate that the removal of damaged proteins by effective proteolysis and the synthesis of new and protective proteins are vital in the preservation of brain homeostasis during periods of increased levels of reactive oxygen species. Last, studies from our laboratory and others have demonstrated that protein synthesis is intricately linked to the rates of protein degradation, with impairment of protein degradation sufficient to decrease the rates of protein synthesis, which has important implications for successfully responding to periods of oxidative stress. Specific neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and stroke, are discussed in this context. Taken t…
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ROS, which are considered markers of oxidative stress, are generated in the cytoplasm of neurons and can cause damage to key cellular components, including DNA, proteins, and lipids, leading to neuronal dysfunction and death.
“It has been proposed that ROS, which are considered markers of oxidative stress, are generated in the cytoplasm of neurons and can cause damage to key cellular components, including DNA, proteins, and lipids, leading to neuronal dysfunction and death (56, 59, 60).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [59]
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- Authors
- Dasuri, K., Zhang, L., & Keller, J. N.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Keller, Jeffrey N.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 62
- Pages
- 170-185
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2044784211
- Cited by
- 371
- References
- 19
- Citations by year
- 2026: 10 · 2025: 29 · 2024: 22 · 2023: 14 · 2022: 29 · 2021: 29 · 2020: 48 · 2019: 35 · 2018: 30 · 2017: 28 · 2016: 25 · 2015: 34 · 2014: 24 · 2013: 13 · 2012: 1
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIA
- Hibernia National Bank/Edward G. Schlieder Chair (J.N.K.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- oxidative stress, neurodegeneration, protein degradation, protein synthesis, proteolytic pathways, reactive oxygen species, neuronal cell death, neuronal dysfunction, brain homeostasis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke
- MeSH terms
- Alzheimer Disease, Amyotrophic Lateral Sclerosis, Humans, Nerve Degeneration, Neurons, Parkinson Disease, Protein Biosynthesis, Reactive Oxygen Species, Oxidative Stress, Proteolysis
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