ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 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 31 papers, 1 of them a synthesis that pooled it.
What it found
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
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- Autophagy-Neuroinflammation Axis in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.Cells · 2026Review
- D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders.Molecular psychiatry · 2025Article
- Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.Molecular neurodegeneration · 2024Article
- Anti-amyloid treatment is broadly effective in neuronopathic mucopolysaccharidoses and synergizes with gene therapy in MPS-IIIA.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
- Neurocognitive testing in a murine model of mucopolysaccharidosis type IIIA.Molecular genetics and metabolism reports · 2023Article
- Redox Imbalance in Neurological Disorders in Adults and Children.Antioxidants (Basel, Switzerland) · 2023Review
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Roles of the Oxytocin Receptor (OXTR) in Human Diseases.International journal of molecular sciences · 2023Review
- Article
- Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets.International journal of molecular sciences · 2022Review
- Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB.The Journal of pharmacology and experimental therapeutics · 2022Article
- Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.The Journal of experimental medicine · 2022Article
- Fluoxetine ameliorates mucopolysaccharidosis type IIIA.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.Frontiers in pharmacology · 2022Review
- Protein aggregation and autophagy dysfunction: new lessons from mucopolysaccharidoses.Autophagy · 2021Article
- Inhibition of Staphylococcus aureus biofilm-forming functional amyloid by molecular tweezers.Cell chemical biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Lysosomal storage diseases (LSDs) are inherited disorders caused by lysosomal deficiencies and characterized by dysfunction of the autophagy-lysosomal pathway (ALP) often associated with neurodegeneration. No cure is currently available to treat neuropathology in LSDs. By studying a mouse model of mucopolysaccharidosis (MPS) type IIIA, one of the most common and severe forms of LSDs, we found that multiple amyloid proteins including α-synuclein, prion protein (PrP), Tau, and amyloid β progressively aggregate in the brain. The amyloid deposits mostly build up in neuronal cell bodies concomitantly with neurodegeneration. Treating MPS-IIIA mice with CLR01, a "molecular tweezer" that acts as a broad-spectrum inhibitor of amyloid protein self-assembly reduced lysosomal enlargement and re-activates autophagy flux. Restoration of the ALP was associated with reduced neuroinflammation and amelioration of memory deficits. Together, these data provide evidence that brain deposition of amyloid proteins plays a gain of neurotoxic function in a severe LSD by affecting the ALP and identify CLR01 as new potent drug candidate for MPS-IIIA and likely for other LSDs.
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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.