ArticlePLoS biology2008
Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed.
- The structure, redox chemistry and motor neuron toxicity of heterodimeric zinc-deficient SOD1-implications for the toxic gain of function observed in ALS.Neurobiology of disease · 2025Article
- Distinct amyloid fibril structures formed by ALS-causing SOD1 mutants G93A and D101N.EMBO reports · 2025Article
- The structure, redox chemistry and motor neuron toxicity of heterodimeric zinc-deficient SOD1-Implications for the toxic gain of function observed in ALS.bioRxiv : the preprint server for biology · 2025Article
- Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1Psychopharmacology · 2025Article
- Effect of Shear and pH on Heat-Induced Changes in Faba Bean Proteins.Foods (Basel, Switzerland) · 2025Article
- Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.Science advances · 2024Article
- A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.International journal of molecular sciences · 2024Review
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS.PLoS biology · 2024Article
- A Simulation Independent Analysis of Single- and Multi-Component cw ESR Spectra.Magnetochemistry (Basel, Switzerland) · 2023Article
- A Zn-dependent structural transition of SOD1 modulates its ability to undergo phase separation.The EMBO journal · 2023Article
- Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice.PloS one · 2023Article
- Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.International journal of molecular sciences · 2022Article
- Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord.Brain : a journal of neurology · 2022Article
- 4-Phenylbutyric Acid (4-PBA) Derivatives Prevent SOD1 Amyloid Aggregation In Vitro with No Effect on Disease Progression in SOD1-ALS Mice.International journal of molecular sciences · 2022Article
- SOD1 gains pro-oxidant activity upon aberrant oligomerization: change in enzymatic activity by intramolecular disulfide bond cleavage.Scientific reports · 2022Article
- Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS.Cells · 2022Article
- MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches.Neural regeneration research · 2022Review
- First Principles Calculation of Protein-Protein Dimer Affinities of ALS-Associated SOD1 Mutants.Frontiers in molecular biosciences · 2022Article
36 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
The nature of the "toxic gain of function" that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS.
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