Dysregulation of Receptor Interacting Protein-2 and Caspase Recruitment Domain Only Protein Mediates Aberrant Caspase-1 Activation in Huntington’s Disease
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.
Minocycline Inhibits Caspase-Independent and -Dependent Mitochondrial Cell Death Pathways in Huntington’s Disease, PNAS 2003
Minocycline is broadly protective in neurologic disease models featuring cell death and is being evaluated in clinical trials. We previously demonstrated that minocycline-mediated protection against caspase-dependent cell death related to its ability to prevent mitochondrial cytochrome c release.
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice
Minocycline mediates neuroprotection in experimental models
of neurodegeneration. It inhibits the activity1–6 of caspase-1,
caspase-3, inducible form of nitric oxide synthetase (iNOS) and
p38 mitogen-activated protein kinase (MAPK).
Inhibition of caspase-1 slows disease progression in amousemodel of Huntington’s disease
Huntington’s disease is an autosomal-dominant progressive
neurodegenerative disorder resulting in specific neuronal loss
and dysfunction in the striatum and cortex1. The disease is
universally fatal, with a mean survival following onset of 15–20
years and, at present, there is no effective treatment.
Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment.
Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits
caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction.
Apoptosis and Caspasesin Neurodegenerative Diseases
Acute and chronic neurodegenerative diseases are illnesses
associated with high morbidity and mortality, and few or no effective options
are available for their treatment.