ArticleMolecular neurodegeneration2010
ALS spinal neurons show varied and reduced mtDNA gene copy numbers and increased mtDNA gene deletions.
Article in Molecular neurodegeneration, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Diagnostic role of circulating cell-free DNA in schizophrenia and neuro-degenerative disorders.Biomarkers in medicine · 2025Review
- Elevated serum circulating cell-free mitochondrial DNA in amyotrophic lateral sclerosis.European journal of neurology · 2024Article
- The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue.Biomolecules · 2024Article
- Quantification of Circulating Cell-Free DNA in Idiopathic Parkinson's Disease Patients.International journal of molecular sciences · 2024Article
- CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions with a distinct signature.Human molecular genetics · 2023Article
- C17orf80 binds the mitochondrial genome to promote its replication.The Journal of cell biology · 2023Article
- Integrative Profiling of Amyotrophic Lateral Sclerosis Lymphoblasts Identifies Unique Metabolic and Mitochondrial Disease Fingerprints.Molecular neurobiology · 2022Article
- Mitochondrial genome variations are associated with amyotrophic lateral sclerosis in patients from mainland China.Journal of neurology · 2022Article
- Mitochondrial protein dysfunction in pathogenesis of neurological diseases.Frontiers in molecular neuroscience · 2022Review
- Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders.International journal of molecular sciences · 2021Review
- Selective Neuron Vulnerability in Common and Rare Diseases-Mitochondria in the Focus.Frontiers in molecular biosciences · 2021Review
- Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research.Molecular neurobiology · 2020Article
- The rise and rise of mitochondrial DNA mutations.Open biology · 2020Review
- From Multi-Omics Approaches to Precision Medicine in Amyotrophic Lateral Sclerosis.Frontiers in neuroscience · 2020Review
- ccf-mtDNA as a Potential Link Between the Brain and Immune System in Neuro-Immunological Disorders.Frontiers in immunology · 2019Review
- The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms.FEBS letters · 2018Review
- Copy Number Variations in Amyotrophic Lateral Sclerosis: Piecing the Mosaic Tiles Together through a Systems Biology Approach.Molecular neurobiology · 2018Review
- A Selection of Important Genes and Their Correlated Behavior in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2018Article
- Sporadic chronic progressive external ophthalmoplegia with single large mitochondrial DNA deletion and neurogenic findings.Journal of neurology · 2017Article
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
backgroundSpinal cord neurons of ALS patients demonstrate reduced cytochrome oxidase histochemical activity, and ALS spinal cord tissues have increased mitochondrial DNA (mtDNA) point mutations and depleted mtDNA levels. It is presently unknown whether mtDNA abnormalities are present in single human ALS neurons.
resultsUsing laser capture microdissection (LCM) we isolated several hundred individual anterior spinal neurons from unfixed, frozen sections of 10 ALS and 7 age-matched CTL cervical spinal cords. DNA from each individual neuron was analyzed with multiplex qPCR for ND2, CO3, and ND4, three mitochondrial DNA genes encoding respiratory proteins. Scatterplots of individual spinal neuron results showed extensive heterogeneity of mtDNA gene levels across 4-5 orders of magnitude that were much more clustered in single Purkinje neurons isolated from CTL cerebella. Plots of ratios of ND4/ND2 and CO3/ND2 showed that many but not all ALS neurons from individuals contained low ratios of these mtDNA genes, implying greater abundances of mtDNA deletions in the major arc. Single CTL cerebellar Purkinje neurons did not contain high levels of apparent mtDNA deletions observed in anterior spinal neurons.
conclusionsAt the time of ALS subjects' deaths, many but not all surviving anterior neurons in their cervical spinal cords have reduced mtDNA gene levels and increased mtDNA deletion abundances that arise for unclear reasons. If these anterior spinal neuron mtDNA gene deficiencies contribute to bioenergetic impairments, reduced synaptic function and increased risk of degeneration, then introduction into mitochondria and expression of intact mtDNA, now available through use of recently developed recombinant human TFAM, may reverse the course of ALS.
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