【摘要】 评述了阿尔茨海默病(Alzheimer’s disease,AD)的多种病因学说,包括胆碱能学说、β-淀粉样级联学说、ABC学说(aging,beta-amyloid,channel)、tau蛋白过度磷酸化学说、氧化应激学说、神经细胞凋亡学说和基因突变学说等.指出AD是多因素引起的病变,其发病机制也必然有多种.由于该病与人体衰老过程密切相关,发病机理复杂,且神经细胞丢失后不具再生能力,这就决定了研究治疗AD有效药物的艰巨性.还指出AD防治工作应重视早期预报和早期干预,发展早期诊断方法包括正电子发射计算机断层扫描、磁共振成像,及血液和尿液中寻找灵敏的生物标志物等技术方法.目前有关AD防治药物包括一线治疗药物、疫苗、尚在研究阶段的药物、辅助性治疗药物、中药以及医疗保健品.前3类药物因疗效或研究结果长期未取得突破性进展,人们开始关注后3类药物对延缓AD的作用及机理.课题组重点开展后3种药物防治AD的作用和机理研究,发现硒代蛋氨酸、辅酶Q-10和中药组分淫羊藿甙对防治AD有好的疗效.综述了目前抗AD药物的研究现状和面临的挑战,提出AD的防治策略是:摒弃针对单一致病因素的治疗思路,从多因素及内在相互联系的系统生物学角度,开展AD防治机制及新药研发.更多还原

【Abstract】 This review briefly introduces multiple theories on Alzheimer’s disease(AD) pathogenesis such as the cholinergic theory,the amyloid-β cascade hypothesis,the ABC theory(aging,β-amyloid,channel),and theories of tau hyperphosphorylation,oxidative stress,neuronal apoptosis,and gene mutation.As AD is closely related with aging,and its pathology is caused by multiple factors,its pathogenesis is bound to be multiple and intricate.Besides,the loss of neurons cannot be regenerated,which suggests that early prediction and intervention in AD treatment is very important.This paper stresses the urgency in developing early diagnosis methods,including positron emission tomography(PET),magnetic resonance imaging(MRI),and sensitive AD biomarkers from blood and urine.The drugs for AD prevention and treatment are generally divided into six types: first-line drugs,vaccines,drugs in the research stage,adjuvant therapy drugs,traditional Chinese medicines,and health products(also known as Medical food).As the top three types have not yet make a breakthrough in AD treatment over a long period of time,people recently turned to pay close attention to the application and mechanism of the other three types of drugs for delaying AD progression.Research in our lab focuses on the effect and mechanism of the latter three types of drugs,and preliminary results show that selenomethionine,coenzyme Q-10,and icariin can significantly prevent AD progression.This paper evaluates the situation and challenge the anti-AD drugs are facing and proposes a change in the strategy for AD prevention: Single-target treatments should be abandoned,and multiple-target idea and inter-related systematic biology should be adopted for studying AD mechanisms and developing new drugs.更多还原