ArticleMolecular neurodegeneration2011
Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Pathomechanisms of behavioral abnormalities in Huntington disease: an update.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- The contribution of preclinical magnetic resonance imaging and spectroscopy to Huntington's disease.Frontiers in aging neuroscience · 2024Review
- An electrophilic fragment screening for the development of small molecules targeting caspase-2.European journal of medicinal chemistry · 2023Article
- ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2.The EMBO journal · 2023Article
- Mitochondrial Bioenergy in Neurodegenerative Disease: Huntington and Parkinson.International journal of molecular sciences · 2023Review
- Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Untangling the Role of Tau in Huntington's Disease Pathology.Journal of Huntington's disease · 2023Review
- Characterization of caspase-2 inhibitors based on specific sites of caspase-2-mediated proteolysis.Archiv der Pharmazie · 2022Article
- Caspase-2 Inhibitor Blocks Tau Truncation and Restores Excitatory Neurotransmission in Neurons Modeling FTDP-17 Tauopathy.ACS chemical neuroscience · 2022Article
- Caspase-2 mRNA levels are not elevated in mild cognitive impairment, Alzheimer's disease, Huntington's disease, or Lewy Body dementia.PloS one · 2022Article
- Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus.Brain sciences · 2021Article
- Uncovering the PIDDosome and caspase-2 as regulators of organogenesis and cellular differentiation.Cell death and differentiation · 2020Review
- Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling.Nature communications · 2019Article
- A soluble tau fragment generated by caspase-2 is associated with dementia in Lewy body disease.Acta neuropathologica communications · 2019Article
- A soluble truncated tau species related to cognitive dysfunction and caspase-2 is elevated in the brain of Huntington's disease patients.Acta neuropathologica communications · 2019Article
- Caspase-2 cleavage of tau reversibly impairs memory.Nature medicine · 2016Article
- An enhanced Q175 knock-in mouse model of Huntington disease with higher mutant huntingtin levels and accelerated disease phenotypes.Human molecular genetics · 2016Article
- Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo.The Journal of biological chemistry · 2015Article
- A Huntingtin-based peptide inhibitor of caspase-6 provides protection from mutant Huntingtin-induced motor and behavioral deficits.Human molecular genetics · 2015Article
- Increased Body Weight of the BAC HD Transgenic Mouse Model of Huntington's Disease Accounts for Some but Not All of the Observed HD-like Motor Deficits.PLoS currents · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHuntington Disease (HD) is a neurodegenerative disorder in which caspase activation and cleavage of substrates, including the huntingtin protein, has been invoked as a pathological mechanism. Specific changes in caspase-2 (casp2) activity have been suggested to contribute to the pathogenesis of HD, however unique casp2 cleavage substrates have remained elusive. We thus utilized mice completely lacking casp2 (casp2-/-) to examine the role played by casp2 in the progression of HD. This 'substrate agnostic' approach allows us to query the effect of casp2 on HD progression without pre-defining proteolytic substrates of interest.
resultsYAC128 HD model mice lacking casp2 show protection from well-validated motor and cognitive features of HD, including performance on rotarod, swimming T-maze, pre-pulse inhibition, spontaneous alternation and locomotor tasks. However, the specific pathological features of the YAC128 mice including striatal volume loss and testicular degeneration are unaltered in mice lacking casp2. The application of high-resolution magnetic resonance imaging (MRI) techniques validates specific neuropathology in the YAC128 mice that is not altered by ablation of casp2.
conclusionsThe rescue of behavioral phenotypes in the absence of pathological improvement suggests that different pathways may be operative in the dysfunction of neural circuitry in HD leading to behavioral changes compared to the processes leading to cell death and volume loss. Inhibition of caspase-2 activity may be associated with symptomatic improvement in HD.
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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.