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Cited by 212Parkinson's Disease Mechanisms and TreatmentsRedox biology and oxidative stressNuclear Receptors and Signaling

The DOI matches its Crossref record; 220 of the 220 references it cites were found in a registry or an index.

The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

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Kumar, Hemant, Lim, Hyung-Woo, More, Sandeep Vasant, Kim, Byung-Wook, Koppula, Sushruta, Kim, In Su, Choi, Dong-Kug·2012·International Journal of Molecular Sciences
DOI 10.3390/ijms130810478PMC PMC3431873
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Abstract

Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.

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Crossref · 10.3390/ijms130810478

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Figures

Figure 1 Schematic representation of the action of free radicals on biological molecules such as lipids, proteins, and DNA. Free radicals react largely in a nonspecific manner with nucleic acids, proteins, and membrane lipids and cause cell injury through various mechanisms as shown. Details are discussed in the main text.
Figure 1 Schematic representation of the action of free radicals on biological molecules such as lipids, proteins, and DNA. Free radicals react largely in a nonspecific manner with nucleic acids, proteins, and membrane lipids and cause cell injury through various mechanisms as shown. Details are discussed in the main text.CC BY · PubMed Central
Figure 2 Generation of free radicals in aging and Parkinson’s disease (PD). A major source of free radicals is mitochondria (mt), mitochondrial complex inhibition either by toxins or aging hampers the mitochondrial respiratory chain, which causes incomplete oxygen reduction, thereby generate reactive species including deleterious superoxide anion (O2−) which is converted to hydrogen peroxide (H2O2) and then finally to hydroxyl radical (·OH) through the Fenton reaction which involves Fe2+ or Cu2+ (not shown). ·OH is a potent inducer of membrane lipid peroxidation. Oxyradicals can also be generated in response to calcium influx. Nitric oxide (NO) interacts with O2− to form peroxynitrite (NO3−), Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to oxidative and nitrosative stress, respectively, which finally causes neurodegeneration. Mitochondrial activity is lost or mitochondrial DNA is damaged during aging, which could lead to generation of ROS. Cytoprotective pathways are activated with the generation of free radicals. Activation of the Nrf2 pathway provides protection by regulating redox balance, whereas the NF-κB pathway causes increased cytokine release which is included in positive feedback to initiate the inflammatory cascade and also through influx of calcium ions inside the extracellular space.
Figure 2 Generation of free radicals in aging and Parkinson’s disease (PD). A major source of free radicals is mitochondria (mt), mitochondrial complex inhibition either by toxins or aging hampers the mitochondrial respiratory chain, which causes incomplete oxygen reduction, thereby generate reactive species including deleterious superoxide anion (O2−) which is converted to hydrogen peroxide (H2O2) and then finally to hydroxyl radical (·OH) through the Fenton reaction which involves Fe2+ or Cu2+ (not shown). ·OH is a potent inducer of membrane lipid peroxidation. Oxyradicals can also be generated in response to calcium influx. Nitric oxide (NO) interacts with O2− to form peroxynitrite (NO3−), Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to oxidative and nitrosative stress, respectively, which finally causes neurodegeneration. Mitochondrial activity is lost or mitochondrial DNA is damaged during aging, which could lead to generation of ROS. Cytoprotective pathways are activated with the generation of free radicals. Activation of the Nrf2 pathway provides protection by regulating redox balance, whereas the NF-κB pathway causes increased cytokine release which is included in positive feedback to initiate the inflammatory cascade and also through influx of calcium ions inside the extracellular space.CC BY · PubMed Central

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Metadata

Authors
Kumar, H., Lim, H.-W., More, S. V., Kim, B.-W., Koppula, S., Kim, I. S., & Choi, D.-K.
Affiliations
Konkuk University (KR)
Corresponding author
Choi, Dong-Kug
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2012-08-21
Volume
13
Issue
8
Pages
10478-10504
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms130810478
PMC
PMC3431873
OpenAlex
W2138898590
Cited by
212
References
220
Citations by year
2026: 4 · 2025: 15 · 2024: 9 · 2023: 16 · 2022: 29 · 2021: 18 · 2020: 18 · 2019: 15 · 2018: 17 · 2017: 14 · 2016: 8 · 2015: 16 · 2014: 11 · 2013: 21 · 2012: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Konkuk University
  • Ministry of Knowledge Economy
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords
free radicals, Parkinson's disease, brain aging, oxidative stress, oxidative damage, dopaminergic neurons, mitochondrial dysfunction, alpha-synuclein aggregation, glial activation, calcium signaling, free iron, NF-κB, Nrf2, glycogen synthase kinase-3β, mitogen-activated protein kinase, superoxide dismutase, catalase, glutathione
MeSH terms
Aging, Animals, Brain, Free Radicals, Humans, Oxidation-Reduction, Parkinson Disease, Oxidative Stress

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