ArticleCell reports2020
Rare Variant Burden Analysis within Enhancers Identifies CAV1 as an ALS Risk Gene.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
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- Neuron-targeted caveolin-1 overexpression attenuates cognitive loss and pathological transcriptome changes in symptomatic Alzheimer's disease models.Signal transduction and targeted therapy · 2025Article
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- Non-coding variation in dementias: mechanisms, insights, and challenges.NPJ dementia · 2025Review
- Emerging Perspectives on Prime Editor Delivery to the Brain.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.Brain : a journal of neurology · 2023Article
- Mendelian Randomization Analysis Reveals Statins Potentially Increase Amyotrophic Lateral Sclerosis Risk Independent of Peripheral Cholesterol-Lowering Effects.Biomedicines · 2023Article
- Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.Nature reviews. Drug discovery · 2023Review
- Review
- Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival.Frontiers in cellular neuroscience · 2023Article
- Simple models to understand complex disease: 10 years of progress fromFrontiers in neuroscience · 2023Review
- The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases.Journal of personalized medicine · 2022Review
- Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis.The Lancet. Neurology · 2022Review
- Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3'UTR protect against ALS.Nature neuroscience · 2022Article
- Article
- Challenge accepted: uncovering the role of rare genetic variants in Alzheimer's disease.Molecular neurodegeneration · 2022Review
- Membrane lipid raft homeostasis is directly linked to neurodegeneration.Essays in biochemistry · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 8 institutions in 5 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Genome-wide association studies localize a large proportion of ALS risk variants within the non-coding genome, but further characterization has been limited by lack of appropriate tools. By designing and applying a pipeline to identify pathogenic genetic variation within enhancer elements responsible for regulating gene expression, we identify disease-associated variation within CAV1/CAV2 enhancers, which replicate in an independent cohort. Discovered enhancer mutations reduce CAV1/CAV2 expression and disrupt MLRs in patient-derived cells, and CRISPR-Cas9 perturbation proximate to a patient mutation is sufficient to reduce CAV1/CAV2 expression in neurons. Additional enrichment of ALS-associated mutations within CAV1 exons positions CAV1 as an ALS risk gene. We propose CAV1/CAV2 overexpression as a personalized medicine target for ALS.
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Registered trials
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.