ArticleProceedings of the National Academy of Sciences of the United States of America2017
Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Shift of the insoluble content of the proteome in the aging mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2023Pooled it
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1Psychopharmacology · 2025Article
- Tunable metastability of condensates reconciles their dual roles in amyloid fibril formation.Molecular cell · 2025Article
- Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases.Current protein & peptide science · 2025Review
- Article
- The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement.Scientific reports · 2024Article
- Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases.Nature reviews. Neuroscience · 2024Review
- Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS.ACS omega · 2024Article
- Article
- Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.Frontiers in molecular neuroscience · 2024Review
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.Human molecular genetics · 2023Article
- Molecular Investigations of Protein Aggregation in the Pathogenesis of Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Calmodulin Binding Domains in Critical Risk Proteins Involved in Neurodegeneration.Current issues in molecular biology · 2022Article
- Ubiquitin homeostasis disruption, a common cause of proteostasis collapse in amyotrophic lateral sclerosis?Neural regeneration research · 2022Article
- Sequence grammar underlying the unfolding and phase separation of globular proteins.Molecular cell · 2022Article
- Review
- Optineurin Deficiency and Insufficiency Lead to Higher Microglial TDP-43 Protein Levels.International journal of molecular sciences · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of different neuropathological subtypes of the disease. Contained within these inclusions are a variety of proteins that do not share obvious characteristics other than coaggregation. However, recent evidence from other neurodegenerative disorders suggests that disease-affected biochemical pathways can be characterized by the presence of proteins that are supersaturated, with cellular concentrations significantly greater than their solubilities. Here, we show that the proteins that form inclusions of mutant SOD1, TDP-43, and FUS are not merely a subset of the native interaction partners of these three proteins, which are themselves supersaturated. To explain the presence of coaggregating proteins in inclusions in the brain and spinal cord, we observe that they have an average supersaturation even greater than the average supersaturation of the native interaction partners in motor neurons, but not when scores are generated from an average of other human tissues. These results suggest that inclusion bodies in various forms of ALS result from a set of proteins that are metastable in motor neurons, and thus prone to aggregation upon a disease-related progressive collapse of protein homeostasis in this specific setting.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.