AEG 3482

An inhibitor of p75NTR- and NRAGE-induced apoptosis

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10mg

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Background

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]

参考文献:
[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.

Protocol

Cell experiment [1]:
Cell lines	PC12 neuronal cells
Preparation method	The solubility of this compound in DMSO is > 14 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	10, 20 and 40 μM, 18 h
Applications	AEG 3482 is a potent antiapoptotic compound. In PC12 neuronal cells AEG 3482 inhibited proapoptotic JNK activity and blocked p75NTR- and NRAGE-induced apoptosis. AEG 3482 inhibited the JNK pathway through increasing HSP70 expression.
参考文献: [1]. Salehi A H, Morris S J, Ho W C, et al. AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70[J]. Chemistry & biology, 2006, 13(2): 213-223.