The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis
Open accessAbstract
Objective: Cerebral atrophy is a correlate of clinical progression in multiple sclerosis (MS). Mitochondria are now established to play a part in the pathogenesis of MS. Uniquely, mitochondria harbor their own mitochondrial DNA (mtDNA), essential for maintaining a healthy central nervous system. We explored mitochondrial respiratory chain activity and mtDNA deletions in single neurons from secondary progressive MS (SPMS) cases. Methods: Ninety‐eight snap‐frozen brain blocks from 13 SPMS cases together with complex IV/complex II histochemistry, immunohistochemistry, laser dissection microscopy, long‐range and real‐time PCR and sequencing were used to identify and analyze respiratory‐deficient neurons devoid of complex IV and with complex II activity. Results: The density of respiratory‐deficient neurons in SPMS was strikingly in excess of aged controls. The majority of respiratory‐deficient neurons were located in layer VI and immediate subcortical white matter (WM) irrespective of lesions. Multiple deletions of mtDNA were apparent throughout the gray matter (GM) in MS. The respiratory‐deficient neurons harbored high levels of clonally expanded mtDNA deletions at a single‐cell level. Furthermore, there were neurons lacking mtDNA‐encoded catalytic subunits of complex IV. mtDNA deletions sufficiently explained the biochemical defect in the majority of respiratory‐deficient neurons. Interpretation: These findings provide evidence that neurons in MS are respiratory‐deficient due to mtDNA deletions, which are extensive in GM and may be induced by inflammation. We propose induced multiple deletions of mtDNA as an important contributor to neurodegeneration in MS. Ann Neurol 2010
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Cites
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
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Self-citationMitochondrial Respiratory-Chain Diseases
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“Respiratory-Deficient Neurons Are Globally Distributed and Not Restricted to Lesions Of the 98 snap-frozen blocks from the MS cases, 81 contained 1 or more of the 3 types of cortical lesions, 96 lesions in total.(25,26) Type I or leukocortical lesions accounted for 39%(37/96), type II lesions accounted for 10%(11/96),…”
InfluentialMitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243
The natural history of multiple sclerosis:a geographically based study
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Self-citationMyelin in the Central Nervous System: Structure, Function, and Pathology
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Neuronal vulnerability and multilineage diversity in multiple sclerosis
Schirmer, L., Velmeshev, D., Holmqvist, S., Kaufmann, M., Werneburg, S., Jung, D., Vistnes, S., Stockley, J. H., Young, A., Steindel, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1404-z · Cited by 638
Self-citationMechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis
Friese, M. A., Schattling, B., & Fugger, L. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.37 · Cited by 628
Metadata
- Authors
- Campbell, G. R., Ziabreva, I., Reeve, A. K., Krishnan, K. J., Reynolds, R., Howell, O., Lassmann, H., Turnbull, D. M., & Mahad, D. J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2010-11-08
- Volume
- 69
- Issue
- 3
- Pages
- 481-492
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2097114048
- Cited by
- 386
- References
- 49
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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