Mixedlineage kinase inhibitors

The c-jun JNK pathway leading to c-jun phosphorylation is involved in neuronal death in response to a wide variety of stimuli, including trophic factor withdrawal, Ab, MPTP glutamate, and NMDA toxicity. Although JNK is a target for preventing neuronal death, upstream kinases in this pathway, in particular, the MLKs are of interest.

CEP-1347 73 is an MLK inhibitor that blocks JNK signaling and has broad neuroprotective activity in a variety of in vitro and in vivo models of neuronal cell death.76 Of relevance to PD, CEP-1347 promotes survival of embryonic dopaminergic neurons77 and blocks MPP + induced cell death and MPTP-dependent increases in nigral JNK pathway activation and loss of SNpc DA neurons and striatal nerve terminals. Evaluation of CEP-1347 in a phase II/III trial for its ability to modify the course of PD showed no benefit of the NCE, and its development for PD was discontinued.75

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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