ArticleMolecular and cellular neurosciences2016
ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling.
Article in Molecular and cellular neurosciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals.Molecules (Basel, Switzerland) · 2024Review
- Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.Molecular systems biology · 2024Article
- Carbamate compounds induced toxic effects by affecting Nrf2 signaling pathways.Toxicology reports · 2024Review
- Upregulated miR-10b-5p as a potential miRNA signature in amyotrophic lateral sclerosis patients.Frontiers in cellular neuroscience · 2024Article
- The evolution of selective autophagy as a mechanism of oxidative stress response: The evolutionarily acquired ability of selective autophagy receptors to respond to oxidative stress is beneficial for human longevity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging.Frontiers in cell and developmental biology · 2022Review
- Role of Nrf2 in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy.Molecular neurodegeneration · 2021Review
- DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity.Cellular and molecular life sciences : CMLS · 2021Review
- SQSTM1eNeurologicalSci · 2021Article
- The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis.Neural regeneration research · 2020Review
- Beyond repression of Nrf2: An update on Keap1.Free radical biology & medicine · 2020Review
- ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway.Autophagy · 2020Article
- Mendelian neurodegenerative disease genes involved in autophagy.Cell discovery · 2020Review
- Retinoic acid worsens ATG10-dependent autophagy impairment in TBK1-mutant hiPSC-derived motoneurons through SQSTM1/p62 accumulation.Autophagy · 2019Article
- SQSTM1/p62: A Potential Target for Neurodegenerative Disease.ACS chemical neuroscience · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders. The Keap1-binding partner and autophagy receptor SQSTM1/p62 has also recently been linked genetically to ALS-FTLD, with some missense mutations identified in patients mapping within or close to its Keap1-interacting region (KIR, residues 347-352). Here we report the effects on protein function of four different disease associated mutations of SQSTM1/p62 which affect the KIR region. Only mutations mapping precisely to the KIR (P348L and G351A) were associated with a loss of Keap1 binding in co-immunoprecipitations comparable to wild-type SQSTM1/p62. These selective effects on Keap1 recognition were entirely rational based on protein structural models. Consistent with impaired Keap1 binding, the P348L and G351A KIR mutants showed reduced ability to activate Nrf2 signalling compared to wild-type SQSTM1/p62 in antioxidant response element (ARE)-luciferase reporter assays. The results suggest that SQSTM1 mutations within the KIR of SQSTM1/p62 contribute to aetiology of some cases of ALS-FTLD through a mechanism involving aberrant expression or regulation of oxidative response genes.
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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.