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Cited by 778Parkinson's Disease Mechanisms and TreatmentsRedox biology and oxidative stressNuclear Receptors and Signaling

Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease

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Trist, Benjamin G., Hare, Dominic J., Double, Kay L.·2019·Aging Cell
DOI 10.1111/acel.13031PMC PMC6826160
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Abstract

Parkinson's disease prevalence is rapidly increasing in an aging global population. With this increase comes exponentially rising social and economic costs, emphasizing the immediate need for effective disease‐modifying treatments. Motor dysfunction results from the loss of dopaminergic neurons in the substantia nigra pars compacta and depletion of dopamine in the nigrostriatal pathway. While a specific biochemical mechanism remains elusive, oxidative stress plays an undeniable role in a complex and progressive neurodegenerative cascade. This review will explore the molecular factors that contribute to the high steady‐state of oxidative stress in the healthy substantia nigra during aging, and how this chemical environment renders neurons susceptible to oxidative damage in Parkinson's disease. Contributing factors to oxidative stress during aging and as a pathogenic mechanism for Parkinson's disease will be discussed within the context of how and why therapeutic approaches targeting cellular redox activity in this disorder have, to date, yielded little therapeutic benefit. We present a contemporary perspective on the central biochemical contribution of redox imbalance to Parkinson's disease etiology and argue that improving our ability to accurately measure oxidative stress, dopaminergic neurotransmission and cell death pathways in vivo is crucial for both the development of new therapies and the identification of novel disease biomarkers.

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  • Excess ROS accumulation or reduced antioxidant levels can directly hamper neuronal synaptic activity and neurotransmission.

    “Excess ROS accumulation or reduced antioxidant levels can directly hamper neuronal synaptic activity and neurotransmission. 8 , 57”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [57]

    The Introduction says ROS accumulation can cause oxidative damage that compromises neuronal function, and the Antioxidant Dysfunction section describes reduced antioxidant defenses. The Figure 4 caption in ‘Dopamine transporters, α-synuclein, and neurotransmitter release’ discusses impaired synaptic dopamine release, but does not establish that excess ROS or reduced antioxidants directly cause that impairment. The claim’s direct link to synaptic activity and neurotransmission is therefore stronger than the paper supports. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Trist, B. G., Hare, D. J., & Double, K. L.
Affiliations
  • The University of Sydney (AU)
  • University of Technology Sydney (AU)
Corresponding author
Double, Kay L.
ORCID
Venue
Aging Cell
Publisher
Wiley
Published
2019-08-20
Volume
18
Issue
6
Pages
e13031-e13031
ISSN
  • 1474-9718 (ISSN-L)
  • 1474-9726
DOI
10.1111/acel.13031
PMC
PMC6826160
OpenAlex
W2969573657
Cited by
778
References
18
Citations by year
2026: 95 · 2025: 148 · 2024: 134 · 2023: 131 · 2022: 147 · 2021: 76 · 2020: 42 · 2019: 5
FWCI
9.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Aging Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • UTS ePRESS (University of Technology Sydney) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, oxidative stress, substantia nigra, aging, dopaminergic neurons, redox imbalance, neurodegeneration, dopamine signaling, cell death pathways, disease biomarkers, disease-modifying therapy, nigrostriatal pathway
MeSH terms
Aging, Animals, Calcium, Humans, Mitochondria, Parkinson Disease, Substantia Nigra, Cellular Senescence, Oxidative Stress

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