ArticleBrain : a journal of neurology2022
Aqp4 stop codon readthrough facilitates amyloid-β clearance from the brain.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- AQP4-dependent enhancement of glymphatic function attenuates tau pathology and neurodegeneration in PS19 mice.Molecular neurodegeneration · 2026Article
- MRI-to-PET synthesis via deep learning for amyloid-β quantification in Alzheimer's disease.European radiology · 2026Article
- Impaired glymphatic function is associated with synaptic loss in cognitive impairment.European journal of nuclear medicine and molecular imaging · 2026Article
- Aquaporin dysfunction and impaired brain interstitial fluid clearance in Alzheimer's disease - an integrative review.Frontiers in cellular neuroscience · 2026Review
- Effect of organismal rhythmic activity on Aβ clearance by the glymphatic system.European journal of medical research · 2025Review
- The Janus face of CaMKII: from memory consolidation to neurotoxic switch in Alzheimer's disease.Archives of toxicology · 2025Review
- Astrocytes as Therapeutic Targets in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Thyroid Hormone T4 Alleviates Traumatic Brain Injury by Enhancing Blood-Brain Barrier Integrity.International journal of molecular sciences · 2025Article
- A route for cerebrospinal fluid flow through leptomeningeal arterial-venous overlaps enables macromolecule and fluid shunting.Nature neuroscience · 2025Article
- Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer's disease.Molecular therapy. Nucleic acids · 2025Review
- Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes.Brain : a journal of neurology · 2025Article
- The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.Nature communications · 2025Article
- The Glymphatic System in Cerebrospinal Fluid Dynamics: Clinical Implications, Its Evaluation, and Application to Therapeutics.Neuro-degenerative diseases · 2025Review
- Glymphatic system: a self-purification circulation in brain.Frontiers in cellular neuroscience · 2025Review
- The RNA Revolution in the Central Molecular Biology Dogma Evolution.International journal of molecular sciences · 2024Review
- Crucial role of Aquaporin-4 extended isoform in brain water Homeostasis and Amyloid-β clearance: implications for Edema and neurodegenerative diseases.Acta neuropathologica communications · 2024Article
- A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias.Human brain mapping · 2024Article
- The impact of astrocytic NF-κB on healthy and Alzheimer's disease brains.Scientific reports · 2024Article
- Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions.Cellular and molecular life sciences : CMLS · 2024Review
- Astrocytes in selective vulnerability to neurodegenerative disease.Trends in neurosciences · 2024Review
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease is initiated by the toxic aggregation of amyloid-β. Immunotherapeutics aimed at reducing amyloid beta are in clinical trials but with very limited success to date. Identification of orthogonal approaches for clearing amyloid beta may complement these approaches for treating Alzheimer's disease. In the brain, the astrocytic water channel Aquaporin 4 is involved in clearance of amyloid beta, and the fraction of Aquaporin 4 found perivascularly is decreased in Alzheimer's disease. Further, an unusual stop codon readthrough event generates a conserved C-terminally elongated variant of Aquaporin 4 (AQP4X), which is exclusively perivascular. However, it is unclear whether the AQP4X variant specifically mediates amyloid beta clearance. Here, using Aquaporin 4 readthrough-specific knockout mice that still express normal Aquaporin 4, we determine that this isoform indeed mediates amyloid beta clearance. Further, with high-throughput screening and counterscreening, we identify small molecule compounds that enhance readthrough of the Aquaporin 4 sequence and validate a subset on endogenous astrocyte Aquaporin 4. Finally, we demonstrate these compounds enhance brain amyloid-β clearance in vivo, which depends on AQP4X. This suggests derivatives of these compounds may provide a viable pharmaceutical approach to enhance clearance of amyloid beta and potentially other aggregating proteins in neurodegenerative disease.
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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.