ArticleNature communications2021
Small-molecule suppression of calpastatin degradation reduces neuropathology in models of Huntington's disease.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- [Systemic Reprogramming of Cellular Senescence: Coordinated Regulation of Metabolism, Epigenetics, and Proteostasis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Review
- A small-molecule stabilizer of the calpastatin-calpain-2 complex restores mitochondrial function and mitigates neurodegeneration.Science advances · 2026Article
- Mitochondrial dysfunction by glyoxalase 1 deficiency disrupts definitive endoderm and alveolar development of human pluripotent stem cells.Experimental & molecular medicine · 2025Article
- Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease.Biomolecules · 2025Review
- NEDD4L induces mitochondrial dysfunction and neurodegeneration by promoting LIPT2 degradation in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alzheimer's disease brain-derived tau extracts show differential processing and transcriptional effects in human astrocytes.iScience · 2025Article
- Down-regulation of neuroprotective protein kinase D in Huntington´s disease.Cell death & disease · 2025Article
- Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5.Nature communications · 2025Article
- Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis.Redox biology · 2025Article
- Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Role of mitochondrial quality control in neurodegenerative disease progression.Frontiers in cellular neuroscience · 2025Review
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.JCI insight · 2024Article
- Uncovering the ferroptosis related mechanism of laduviglusib in the cell-type-specific targets of the striatum in Huntington's disease.BMC genomics · 2024Article
- Enoyl coenzyme a hydratase 1 attenuates aortic valve calcification by suppressing Runx2 via Wnt5a/CaJournal of cell communication and signaling · 2024Article
- Latest assessment methods for mitochondrial homeostasis in cognitive diseases.Neural regeneration research · 2024Review
- Neuron-targeted overexpression of caveolin-1 alleviates diabetes-associated cognitive dysfunction via regulating mitochondrial fission-mitophagy axis.Cell communication and signaling : CCS · 2023Article
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.bioRxiv : the preprint server for biology · 2023Article
- Neurotoxic properties of the Zika virus envelope protein.Experimental neurology · 2023Article
- Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System.Biomolecules · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial dysfunction is a common hallmark of neurological disorders, and reducing mitochondrial damage is considered a promising neuroprotective therapeutic strategy. Here, we used high-throughput small molecule screening to identify CHIR99021 as a potent enhancer of mitochondrial function. CHIR99021 improved mitochondrial phenotypes and enhanced cell viability in several models of Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Notably, CHIR99201 treatment reduced HD-associated neuropathology and behavioral defects in HD mice and improved mitochondrial function and cell survival in HD patient-derived neurons. Independent of its known inhibitory activity against glycogen synthase kinase 3 (GSK3), CHIR99021 treatment in HD models suppressed the proteasomal degradation of calpastatin (CAST), and subsequently inhibited calpain activation, a well-established effector of neural death, and Drp1, a driver of mitochondrial fragmentation. Our results established CAST-Drp1 as a druggable signaling axis in HD pathogenesis and highlighted CHIR99021 as a mitochondrial function enhancer and a potential lead for developing HD therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.