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Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 activation in Huntington's disease
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 25(50)
- Publication Year :
- 2005
-
Abstract
- Caspase-1 plays a role in the pathogenesis of a variety of neurological diseases. Caspase-1 activation is an early event in models of Huntington's disease (HD). However, mechanisms regulating the activation of this apical caspase in cell death are not known. Receptor interacting protein-2 (Rip2) and caspase recruitment domain (CARD) only protein (Cop) are two CARD proteins with significant homology to the caspase-1 CARD and modulate caspase-1 activation in inflammation. Rip2 is a caspase-1 activator, and Cop is a caspase-1 inhibitor. We demonstrate in models of HD that caspase-1 activation results from dysregulation of caspase-1 activation pathways. Associated with disease progression, we detect elevation of the caspase-1 activator Rip2 and reduction of the caspase-1 inhibitor Cop. Knocking down endogenous Rip2/Cop respectively results in reduced/increased sensitivity to neurotoxic stimuli. Our data provide evidence that caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop, and alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntington's disease.
- Subjects :
- Programmed cell death
Caspase 1
Inflammation
Protein Serine-Threonine Kinases
Pathogenesis
Mice
Huntington's disease
Receptor-Interacting Protein Serine-Threonine Kinase 2
Neurobiology of Disease
medicine
Animals
Humans
Receptor
Caspase
Cells, Cultured
Neurons
biology
Cell Death
Activator (genetics)
General Neuroscience
Stem Cells
medicine.disease
Caspase Inhibitors
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Cell biology
Enzyme Activation
Huntington Disease
Receptor-Interacting Protein Serine-Threonine Kinases
Cancer research
biology.protein
medicine.symptom
Carrier Proteins
HeLa Cells
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 25
- Issue :
- 50
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....b40d1086bf1915fdff063f15fd7eeb8a