报告题目：Neuroprotective effect of Artemisinin and its implication in the treatment of Alzheimer's Disease
报 告 人：郑文华 教授（澳门大学健康科学学院）
郑文华博士，澳门大学健康科学学院教授，独立PI，博后/博士生导师。86年毕业于中山医科大学，获医学学士学位，02年毕业于加拿大McGill大学，获药理学博士学位；92年到95年在美国Rochester大学医学院做客座科学家（Visiting Scientist），美国国立健康研究院客座研究员（Visiting Fellow）。02-06年在McGill大学Douglas Hospital Research Center带领一个由几个博士后及博士研究生组成的课题组研究生长因子和自然产物（植物银杏、红酒和绿茶提取物等）对神经细胞保护的分子作用机制。06年中山大学“百人计划”引进回国，任中山大学药理/眼科博导，神经药理PI组主任，15年加入澳门大学，17 年破格提升为教授。
郑文华教授提出了谷氨酸能在受体水平通过抑制生长因子受体磷酸化而介导细胞毒性的假说，并在细胞水平及整体动物验证了这一假说；系统地研究了神经营养因子（如IGF-1/NGF /BDNF/NT3/NT4等）促进神经细胞的存活的分子机制；证明PI3K/Akt/FoxO等是神经营养因子的下游靶标；研究了FoxO的下游靶标及其在神经系统的生物学功能。近年发现了青蒿素具有中枢神经保护药物的属性，可能成为中枢神经治疗用药。已发表一百多篇SCI论文，文章被引用>4500次，相关成果已发表于《Free Radical Biology and Medicine》（IF 6.0/6.34）和《Redox Biology》（IF 7.8/9.04）等自由基权威期刊并申请了多个专利。
Alzheimer's Disease (AD), characterized by theprogressive loss of cognitive function, is the most common neurodegenerative disorder. It is marked by the occurrence of neuronal loss and by the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (Tau hyperphosphorylation).AD etiology is still unknown, and currently there is no effective treatment to cure or prevent it. In recent years, neuroprotection has attractedwidespread attentionand there is an urgent need for a safe and effective neuroprotective agent able to improve and delaythe progression of Alzheimer's disease.Artemisinin and its derivatives are safe and effective first-line 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 isaffordable, 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/SNP/H2O2-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 revealedthat 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 resultswere 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 reversedseveralpathological changes in AD mice. It reduced neuronal cell death, Aβ deposit and tau phosphorylation, increased neuronal regeneration and cholinergic function, inhibitedthe inflammatory response and over-activation of glial cells. These results demonstrate that artemisinin and its derivatives can improve various symptoms and pathological changes of AD through neuroprotection, reducing amyloidogenesis/tau hyperphosphorylation andinflammation, functioning as a new multi-target neuroprotective/anti-AD agent. These findings support the potential application of artemisinin and its derivatives on the prevention and treatment of neurodegenerative diseases such as AD.