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Published on: September 28, 2019
Misfolded SOD1 and ALS: zeroing in on mitochondria
Sarah Pickles1, Christine Vande Velde
1Centre d'excellence en neuromique de l'Université de Montréal, Centre de recherche du CHUM (CRCHUM), Montréal, QC, Canada.
Summary
Mutations in SOD1 (superoxide dismutase 1) cause familial ALS. New antibodies detect misfolded SOD1, revealing its connection to mitochondria.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Mutations in the SOD1 gene are linked to familial Amyotrophic Lateral Sclerosis (ALS).
- These mutations lead to the formation of abnormal, misfolded SOD1 protein conformers.
- Identifying and targeting these misfolded proteins is crucial for understanding ALS pathogenesis.
Purpose of the Study:
- To review novel antibodies developed for detecting misfolded SOD1.
- To explore the role of mitochondria as a cellular target for misfolded SOD1.
- To provide insights into potential therapeutic strategies for SOD1-related ALS.
Main Methods:
- Review of recent scientific literature on SOD1 mutations and antibodies.
- Analysis of in vitro and in vivo studies utilizing new anti-misfolded SOD1 antibodies.
- Examination of evidence linking misfolded SOD1 to mitochondrial dysfunction.
Main Results:
- New antibodies enable specific detection of misfolded SOD1.
- Mitochondria are identified as a key cellular compartment affected by misfolded SOD1.
- The findings support a common pathogenic pathway involving SOD1 misfolding and mitochondrial interaction.
Conclusions:
- Novel antibodies are valuable tools for studying SOD1 misfolding in ALS.
- Mitochondrial dysfunction is a significant consequence of SOD1 protein misfolding.
- Targeting the interaction between misfolded SOD1 and mitochondria may offer therapeutic avenues for ALS.
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