Enzymic Activities in Spinal Cord Injury

Calpains are a family of calcium-dependent cysteine proteases that are widely expressed in brain and spinal cord tissues. These enzymes have been implicated in cell death in spinal cord injury (Ray et al., 2003 Buki et al., 2003). Calpain activity is modulated by an endogenous protein inhibitor called calpastatin. Overactivation... 

Today, with the exception of bone marrow for hematopoietic reconstitution, therapeutic cellular transplantation is an emerging technology. In recent years novel approaches in the potential restoration of function through cellular transplantation have included the use of fetal human or xenogeneic neural tissue for Parkinson s disease, ectopically implanted pancreatic islets for diabetes, Schwann cells and olfactory ensheathing glia for spinal cord injury, encapsulated chromaffin cells for pain, and various types of stem cells for the treatment of diabetes, cardiac disease, and central nervous system injuries or disease [2], There have also been trials of encapsulated cells to provide enzymes that either remove toxic products or provide activation of prodrugs to therapeutics, usually anticancer derivatives. 

Neurochemical Aspects of Spinal Cord Injury Table 4.1 Effect of Ca influx on enzymic activities in injured spinal cord... 

As previously discussed, the COX-2 inhibitors have selectivity for inhibition of the COX-2 enzyme, which has low constitutive activity but is highly inducible at sites of tissue injury. In addition to the peripheral role of COX-2 in inflammation, COX-2 may play an important role in the CNS. COX-2 is expressed constitutively in some excitatory neurons in the brain and spinal cord and is induced in traumatic brain injury such as that induced by ischemia and seizures. It has been hypothesized that COX-2 may also be involved in neurodegen-erative diseases, since COX-2 inhibitors have shown some positive effects in Alzheimer s disease. Thus, the mechanism of action of COX-2 inhibitors may involve brain and spinal cord sites as well as local sites of injury. 

Caspases, a family of aspartate-specific cysteine proteases, are essential in the initiation and execution of apoptosis (Creagh et al., 2003 Cohen, 1997). They are expressed as inactive proenzymes (zymogens) that become active during apoptosis. Out of 14 caspase enzymes, caspase-3 appears to be the major effector of neuronal apoptosis induced by a variety of stimuli as well as traumatic injuries (Fig. 4.4). A role for caspase-3 in injury-induced neuronal cell death has been established using semispecific peptide caspase inhibitors. Caspases not only cleave other downstream caspases but also a variety of enzymes, cytokines, cytoskeletal, nuclear, and cell cycle regulatory proteins (Cohen, 1997). Their activities in brain and spinal cord tissues are regulated by the occurrence in zymogens form, by members of Bcl-2 family, and certain cellular inhibitor of apoptosis proteins (cIAPs). 

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