DDP-4抑制剂治疗阿尔茨海默病的机制研究进展  

Progress of Researches on Mechanisms of DDP-4 Inhibitors Intervention of Alzheimer's Disease

作　　者：陈本伟 董齐[1] 伊然[2] 赵静[1] 曹海玲[1] 郑晓荣[1] 张译丹[1] 唐晶[3] 

机构地区：[1]哈尔滨医科大学附属第一医院神经内科,150001 [2]哈尔滨医科大学附属第一医院内分泌科,150001 [3]吉林医药学院附属医院神经内科,132013

出　　处：《中国临床神经科学》2016年第1期89-95,共7页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金资助项目(编号:81500912);黑龙江省自然科学基金资助项目(编号:QC2011C117);黑龙江省教育厅面上项目(编号:11551223;12511241);黑龙江省卫生厅面上项目(编号:2009-059)

摘　　要：阿尔茨海默病(AD)是一种渐进的神经退行性疾病,逐渐恶化的记忆和认知功能最终导致AD患者无法正常独立生活。流行病学研究发现2型糖尿病(T2DM)患者容易罹患AD。DDP-4抑制剂是一种治疗糖尿病的药物,DPP-4抑制剂主要通过抑制肠促胰高糖素样-1(GLP-1)的降解,增加循环中GLP-1含量,从而降低空腹血糖。目前研究发现DDP-4抑制剂可以用于治疗AD,DDP-4抑制剂通过增高GLP-1而降低Aβ水平、减少tau蛋白磷酸化、减轻炎症反应而发挥神经保护作用。关于DDP-4抑制剂在AD治疗中的确切分子机制仍有待进一步阐明。文中对DDP-4抑制剂治疗AD的机制研究进展做一综述。Alzheimer＇s disease（AD） is a progressive neurodegenerative disorder that gradually deteriorates memory and cognitive skills eventually affecting normal independent daily living in affected individuals. Epidemiological evidence has shown that adults who develop type 2 diabetes mellitus（T2DM） at later stages in life are at higher risk of developing AD. Dipeptidyl peptidase Ⅳ（DPP-Ⅳ） inhibitors is a new type of oral hypoglycemic agents for the treatment of patients with type 2 diabetes. Inhibition of the enzyme DPP-Ⅳ results in decrease of high levels of fast blood glucose in patients with type 2 diabetes by inhibiting the degradation of glucagon-like peptide-1（GLP-1） and enhancing GLP-1 bioactivity. Recent new drugs anti-T2DM（DDP-4 inhibitors） could reverse the pathological features. DPP-4 inhibition demonstrates neuroprotective effects that decrease amyloid beta（Aβ） peptide and tau phosphorylation, attenuation inflammation. However, further investigation is required to elucidate the neurochemical and molecular mechanisms involved in the neuroprotective effects of DDP-4 inhibitors. The progress of researches on mechanisms of DDP-4 inhibitors intervention of AD were reviewed.

关 键 词：阿尔茨海默病 2型糖尿病 DDP-4抑制剂 Β淀粉样蛋白 磷酸化TAU蛋白 炎症反应 

分 类 号：R749.1[医药卫生—神经病学与精神病学]