GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, THE PUTATIVE TARGET OF THE ANTIAPOPTOTIC COMPOUNDS CGP-3466 AND R-(-)-DEPRENYL

R-(-)-Deprenyl (Selesline) represents one of the drugs currently used for the treatment of Parkinson's disease. This compound was shown to p rotect neurons or glias from programmed cell death in a variety of mod els, The mechanism of action of neuroprotection as well as inhibition of apoptosis remains elusive, CGP 3466 is a structurally related analo g of R-(-)-deprenyl that exhibits virtually no monoamine oxidase type B inhibiting activity but is neuroprotective in the picomolar concentr ation range, We showed specific binding of CGP 3466 to glyceraldehyde- 3-phosphate dehydrogenase by affinity binding, by affinity labeling, a nd by means of BIAcore(R) technology. Apoptosis assays based on the hu man neuroblastoma cell line PAJU established the importance of this in teraction for mediating drug-induced inhibition of programmed cell dea th.