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Mitochondria in sporadic amyotrophic lateral sclerosis
R H Swerdlow1, J K Parks, D S Cassarino
1Department of Neurology, University of Virginia Health Sciences Center, 1 Hospital Drive, Charlottesville, Virginia 22908, USA.
Experimental Neurology
|September 23, 1998
Summary
Mitochondrial DNA (mtDNA) abnormalities contribute to amyotrophic lateral sclerosis (ALS). Transferring mtDNA from ALS patients to cells replicated disease-like mitochondrial defects, supporting mtDNA
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mitochondrial dysfunction is observed in amyotrophic lateral sclerosis (ALS) but the underlying cause remains unclear.
- Investigating the role of mitochondrial DNA (mtDNA) in ALS pathogenesis is crucial.
Purpose of the Study:
- To determine if mitochondrial DNA (mtDNA) aberrations contribute to amyotrophic lateral sclerosis (ALS) pathogenesis.
- To investigate the functional consequences of ALS-associated mtDNA in a cellular model.
Main Methods:
- Transferring mitochondrial DNA (mtDNA) from ALS patients into mtDNA-depleted human neuroblastoma cells to create cytoplasmic hybrids (cybrids).
- Analyzing electron transport chain (ETC) function, free radical scavenging enzyme activity, calcium homeostasis, and mitochondrial ultrastructure in resulting ALS cybrids.
Main Results:
- ALS cybrids displayed impaired electron transport chain (ETC) functioning.
- Elevated free radical scavenging enzyme activities and disrupted calcium homeostasis were observed in ALS cybrids.
- Alterations in mitochondrial ultrastructure consistent with disease-related changes were identified.
Conclusions:
- Expression of ALS-associated mitochondrial DNA (mtDNA) in cybrids recapitulated key defects found in ALS patients and models.
- These findings support a significant pathophysiological role for mitochondrial DNA (mtDNA) mutations in the development of amyotrophic lateral sclerosis (ALS) in some individuals.