Alzheimer's Disease (AD), characterized by the progressive loss of cognitive function, is the most common neurodegenerative disorder. It is marked by the occurrence of neuronal loss, the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles. AD etiology is still unknown, and currently there is no effective treatment to cure or prevent it. Artemisinin and its derivatives are safe and effective antimalarials, which have been used for decades in the clinic saving millions of lives. We have recently discovered that, artemisinin has a neuroprotective effect. Since it is affordable, safe and able tocross the blood-brain barrier, this discovery offers new promising therapeutic indications for artemisinin in diseases of the central nervous system. We have found that artemisinin/artemether promoted the survival of several neuronal cells. In fact, pretreatment of PC12 cells with artemisinin/artemether significantly inhibited Aβ1-42-induced cell death, reduced intracellular reactive oxygen species (ROS) production, prevented mitochondrial membrane potential loss and reduced LDH release and caspase 3/7 activation. Western blot analysis revealed that artemisinin/artemether stimulatedthe phosphorylation/activation of ERK, AMPK and CREB while inhibition of the ERK/ AMPK signaling pathways, by eitherERK pathway inhibitor PD98059/AMPK inhibitor Compound C, reduced the expression of ERK/AMPK with siRNA blocking the protective effect of artemisinin/ artemether. Similar results were obtained in other neuronal cells and primary cultured neurons. These findings suggest that artemisinin/ artemether is a potential neuroprotective agent that inhibits various toxin-induced cell death by activating signaling pathways such as ERK/AMPK/ autophagy. In addition, artemisinin/artemether significantly improved the cognitive impairment and reversed several pathological changes in AD mice. It reduced neuronal cell death, Aβ deposit and tau phosphorylation. These findings support the potential application of artemisinin and its derivatives on the prevention and treatment of neurodegenerative diseases such as AD
Dr. Wenhua Zheng, Professor, Principle Investigator in Faculty of Health Science, University of Macau, leading a group of scientists working on aging and neuronal degenerative disorders. He is a Section Editor for Encyclopedia of Gerontology and Population Aging; a Lead Guest Editor and Editor for several journals. Grant Reviewer for NSFC, Poland and CIHR in Canada. He is an Honorary Professor at the University of Queensland (QS45) and an Adjunct Professor/ visiting Prof at RMIT University and other universities. Dr Zheng has published >150 papers which have been cited over 6500 times
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