Screening of neuroprotective agents from Chinese medicinal herbs by protein kinases

Abstract

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder and its prevalence is about 10% in people aged over 65. As the effectiveness of current treatment for AD (cholinesterase inhibitor) is not the only one target, 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 (Aβ) peptides found in the cortex of AD brain. Aβ 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 and JNK) mediate Aβ-triggered neuronal apoptosis. On the other hand, activation of kinases in survival signaling pathway (PDK-1 and Akt) can inhibit apoptosis. It is hypothesized that neuroprotection can be achieved by inhibition on pro-apoptotic pathways or activation of survival pathways. By western blotting, 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) decreases Aβ-triggered PKR and JNK phosphorylation. All these extracts can protect neurons against Aβ 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 medicinal herbs. Supported by This work is supported by Area of Excellence (AoE/P-10/01), Seed Funding for Basic Research to RCCC (2002-2003; 2003-2004), and HKU Technology Transfer Seed Funding, The University of Hong Kong, to RCCC, WHY, SYZ and KFS.