ArticleMolecular neurodegeneration2017
Caspase vinyl sulfone small molecule inhibitors prevent axonal degeneration in human neurons and reverse cognitive impairment in Caspase-6-overexpressing mice.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Optimized detection of caspase-6 activation in a murine inflammation model to inform neurodegenerative disease therapies.PloS one · 2026Article
- Organosulfur Compounds: Potential Therapeutics for Parkinson's Disease.CNS & neurological disorders drug targets · 2026Review
- An NMR sample preparation case study: Considerations for the self-destructive protease caspase-6.PloS one · 2025Article
- Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.ACS catalysis · 2024Article
- Inhibition of Apoptosis in a Model of Ischemic Stroke Leads to Enhanced Cell Survival, Endogenous Neural Precursor Cell Activation and Improved Functional Outcomes.International journal of molecular sciences · 2024Article
- Metal-free hydrosulfonylation of α,β-unsaturated ketones: synthesis and application of γ-keto sulfones.RSC advances · 2022Article
- Caspase-1 inhibition improves cognition without significantly altering amyloid and inflammation in aged Alzheimer disease mice.Cell death & disease · 2022Article
- Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer-type pathogenesis.Aging cell · 2022Article
- Non-Canonical Roles of Apoptotic Caspases in the Nervous System.Frontiers in cell and developmental biology · 2022Review
- RNA N6-Methyladenosine Modifications and Its Roles in Alzheimer's Disease.Frontiers in cellular neuroscience · 2022Review
- De Novo Molecular Design of Caspase-6 Inhibitors by a GRU-Based Recurrent Neural Network Combined with a Transfer Learning Approach.Pharmaceuticals (Basel, Switzerland) · 2021Article
- A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson's Disease.Molecules (Basel, Switzerland) · 2021Article
- Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits.Cell death & disease · 2021Article
- Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice.Acta neuropathologica communications · 2019Article
- Identification of Allosteric Inhibitors against Active Caspase-6.Scientific reports · 2019Article
- Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis.The Journal of biological chemistry · 2019Article
- Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.Scientific reports · 2018Article
- Novel therapeutic target against Alzheimer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe activation of the aspartate-specific cysteinyl protease, Caspase-6, is proposed as an early pathogenic event of Alzheimer disease (AD) and Huntington's disease. Caspase-6 inhibitors could be useful against these neurodegenerative diseases but most Caspase-6 inhibitors have been exclusively studied in vitro or show acute liver toxicity in humans. Here, we assessed vinyl sulfone small molecule peptide caspase inhibitors for potential use in vivo.
methodsThe IC
resultsVinyl sulfone NWL-117 caspase inhibitor has a higher selectivity against Caspase-6, -4, -8, -9, and -10 whereas NWL-154 has higher selectivity against Caspase-6, -8, and -10. The half-maximal inhibitory concentrations (IC
conclusionsNWL peptidic vinyl methyl sulfone inhibitors are potent, non-toxic, blood-brain barrier permeable, and irreversible caspase inhibitors with neuroprotective effects in HCT116 cells, in primary human CNS neurons, and in Caspase-6 mice. These results highlight the therapeutic potential of vinyl sulfone inhibitors as caspase inhibitors against neurodegenerative diseases and sanction additional work to improve their selectivity against different caspases.
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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.