Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine

Abstract

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder affecting quite a lot of elderly in different countries. Current treatment for AD depends on cholinesterase inhibitor. However, its effectiveness is quite disappointing. Therefore, there is an urgent need to search for alternate treatment and neuroprotection is a possible strategy. One of the critical pathological factors in AD is the accumulation of beta-amyloid (A ) peptides found in the cortex of AD brain. A peptides have been shown to induce cell death in cultured neurons and are often used as a model toxin to study the pathogenesis of AD. Previous studies have shown that stress kinases (such as PKR, JNK, p38 MAPK and GSK3 ) mediate A -triggered neuronal apoptosis. On the other hand, both kinases PDK-1 and Akt in survival signaling pathway can inhibit apoptosis. It is hypothesized that neuroprotection can be achieved by inhibition on pro-apoptotic pathways or activation of survival pathways. By western blot analysis, we found that polysaccharides from Nerium indicum (Oleander) activate the PDK-1- Akt survival signaling pathway while the extract from Lycium barbarum (Gou-Qi-Zi) inhibits A -triggered PKR and JNK phosphorylation. All these extracts can protect neurons against A toxicity by inhibition on caspase-3 activity. In conclusion, it is possible to make use of protein kinases to screen potential neuroprotective agents from Chinese medicine. Acknowledgement: This work is supported by Area of Excellence (AoE/P-10/01).