New inhibitors of caspase-2, useful for treatment of neurodegenerative diseases, are double-stranded short interfering RNAs specific for caspase-2 mRNA

摘要

Inhibitors (A) of caspase-2, comprising isolated duplexes of short interfering RNA (siRNA), are new. They target specifically the mRNA of caspase-2, resulting in reduction or suppression of the expression of caspase-2, and contain the strands (a) (2) and (3) or (b) (8) and (9). caccuccuagagaaggaca-dTdT (2) uguccuucucuaggaggug-dTdT (3) caucuucuggagaaggaca-dTdT (8) uguccuucuccagaagaug-dTdT (9) where dT = deoxythymidine. ACTIVITY : Nootropic; Neuroprotective; Antiparkinsonian; Anticonvulsant; Cerebroprotective. No details of tests for these activities are given. MECHANISM OF ACTION : Inhibiting expression of caspase-2, thus inhibiting apoptotic, necrotic and autophagic mechanisms of cell death. The siRNA containing sequences (2) and (3) was designed to target region 185-203 of the murine caspase-2 mRNA. Murine cortical neurons treated with it produced no caspase-2, as determined by Western blotting. caccuccuagagaaggaca-dTdT (2) uguccuucucuaggaggug-dTdT (3) where dT = deoxythymidine.