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 Cytochrome C Release and Delays Progression (Mayo/Elsevier)

Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation.

Role of Caspase 1 in Neurologic Disease, JAMA Neurology 2000

In recent years substantial advances have taken place in understanding the mechanistic pathways mediating neuronal cell death in a variety of neurologic diseases. Since the central nervous system (CNS) has little, if any, power of functional neuronal regeneration, prevention of neuronal cell death is an important target of modern neurotherapeutics.