| abstract |
The present invention is directed to an isolated and purified enzyme designated apopain, methods of using apopain to screen for compounds which modulate the activity of apopain, and compounds identified by the screens. A synthetic DNA molecule encoding full length apopain is prepared from the purified enzyme. The synthetic apopain-encoding DNA is formulated so as to optimize expression in a variety of recombinant hosts. The DNA clones produce recombinant full-length apopain and derivatives thereof. Purified native apopain and recombinant apopain are useful for identifying modulators of apopain activity and hence modifiers of pathological conditions related to the pro-inflammatory or pro-apoptotic effects of apopain. Apopain antisense molecules are useful for therapeutically reducing or eliminating the pro-inflammatory or pro-apoptotic effects of apopain, whereas gene transplantation or gene therapy with apopain is useful for enhancing the pro-inflammatory or pro-apoptotic effects of apopain. These therapies are beneficial in the treatment of immune, proliferative and degenerative diseases including, but not limited to, immune deficiency syndromes (such as AIDS), autoimmune diseases, pathogenic infections, cardiovascular and neurological injury, alopecia, aging, cancer, Parkinson's disease and Alzheimer's disease. |