AEG3482 is a small-molecule inhibitor of Jun kinase (JNK)-dependent apoptosis. [1,2]
Jun kinases, also called Jun N-terminal kinase stress-activated protein kinases. Activation of the JNK signaling pathway is a major event in neuronal apoptosis. This is proved by pathological specimens from Alzheimer’s disease, as well as samples from mouse models of Alzheimer’s and Huntington’s disease, reveal activated JNK. [2]
AEG3482 blocks apoptosis induced by the p75 neurotrophin receptor (p75NTR) or NRAGE, which is p75NTR’s cytosolic interactor,. AEG3482 inhibits proapoptotic JNK activity. AEG3482 induces production of heat shock protein 70 (HSP70) which is an endogenous inhibitor of JNK. HSP70 accumulation is required for the AEG3482-induced JNK blockade. [1]
As described, activation of C-jun N-terminal kinase (JNK) signaling is associated with neuronal cell death. AEG3482 interacts with heat shock protein 90 leading to inhibition of JNK and blockade of neuronal apoptosis. So AEG3482 can serve as useful tools for basic research, and it may have therapeutic potential for the treatment of acute and chronic neurological disorders. In the neuropathologicalstate, the chaperone-mediated stress response may be primed for response to Hsp90 inhibitors; and AEG3482, may be selective neuroprotective agents.[1,2]
References:
[1]Salehi AH, Morris SJ, Ho WC, etal. , AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70. Chem Biol. 2006 Feb;13(2):213-23.
[2] Gallo KA. Targeting HSP90 to halt neurodegeneration. Chem Biol. 2006 Feb;13(2):115-6.