ReviewFrontiers in cellular neuroscience2022
Evidence That Substantia Nigra Pars Compacta Dopaminergic Neurons Are Selectively Vulnerable to Oxidative Stress Because They Are Highly Metabolically Active.
Review in Frontiers in cellular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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Who cites it
66 citing papers in PubMed, 89 citations in OpenAlex.
- Engineering functional ventral midbrain dopaminergic neurons in human organoids through WNT modulation and bioreactor culture.Molecular psychiatry · 2026Article
- Duration-dependent mild heat stress attenuates mercury-induced Neuroreproductive and oxidative toxicity in Drosophila melanogaster via hormetic mechanisms.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Fungal-Derived Decahydrofluorene Alkaloids Promote Mitochondrial Resilience and Neuroprotection in Cellular and Animal Models of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- Chronic Methamphetamine Administration Increases Mitochondrial Density and Impairs Mitochondrial Function in the Substantia Nigra Pars Compacta.Journal of neurochemistry · 2026Article
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- Reviving mitochondria to restore the mind: stem cell-based bioenergetic rescue in Parkinson's disease.Neurodegenerative disease management · 2026Review
- Potential Relevance of Amazonian Diet Components in Parkinson's Disease: An Integrative Review with Multivariate Analysis.Nutrients · 2026Review
- Overcoming Oxidative Stress in Parkinson's Disease: NADPH Oxidase 4 (NOX4) as a Potential Therapeutic Target.Antioxidants (Basel, Switzerland) · 2026Review
- Mitochondrial dysfunction in sleep deprivation.Metabolic brain disease · 2026Review
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- TMBIM6 enhances dopaminergic neuron survival by modulating the IRE1a pathway in Parkinson's disease.Cell death & disease · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Decoding the RNA Shield: HNRNPC and YTHDF2 Act as Guardians of Neurons in Parkinson's Disease.Neurotoxicity research · 2026Review
- Advancing AADC deficiency therapy through MR-guided multisite delivery of AAV2-hAADC to dopaminergic and serotonergic pathways in the brainstem.Molecular therapy. Advances · 2026Article
- Redefining Parkinson's Disease management: the synergistic role of neurotrophic factors and mitochondria.Cellular and molecular life sciences : CMLS · 2026Review
- Unraveling Parkinson's disease: The mystery of mitochondria and the role of aging.Genes & diseases · 2026Review
- Glycolytic Specialization Shapes Neuronal Physiology and FunctionbioRxiv : the preprint server for biology · 2026Article
- An in vivo and in vitro spatiotemporal profile of human midbrain development.Nature communications · 2026Article
- Sources of Oxidative Stress in Parkinson's Disease: Pathways and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are 400-500 thousand dopaminergic cells within each side of the human substantia nigra pars compacta (SNpc) making them a minuscule portion of total brain mass. These tiny clusters of cells have an outsized impact on motor output and behavior as seen in disorders such as Parkinson's disease (PD). SNpc dopaminergic neurons are more vulnerable to oxidative stress compared to other brain cell types, but the reasons for this are not precisely known. Here we provide evidence to support the hypothesis that this selective vulnerability is because SNpc neurons sustain high metabolic rates compared to other neurons. A higher baseline requirement for ATP production may lead to a selective vulnerability to impairments in oxidative phosphorylation (OXPHOS) or genetic insults that impair Complex I of the electron transport chain. We suggest that the energy demands of the unique morphological and electrophysiological properties of SNpc neurons may be one reason these cells produce more ATP than other cells. We further provide evidence to support the hypothesis that transcription factors (TFs) required to drive induction, differentiation, and maintenance of midbrain dopaminergic neural progenitor cells which give rise to terminally differentiated SNpc neurons are uniquely involved in both developmental patterning and metabolism, a dual function unlike other TFs that program neurons in other brain regions. The use of these TFs during induction and differentiation may program ventral midbrain progenitor cells metabolically to higher ATP levels, allowing for the development of those specialized cell processes seen in terminally differentiated cells. This paper provides a cellular and developmental framework for understanding the selective vulnerability of SNpc dopaminergic cells to oxidative stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.