β-Amyloid （Aβ） over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer＇s disease （AD）.Studies on them may help elucidate the precise molecular pathogenesis of AD.Until now,although tau protein and Aβ remain the foci of AD research,the etiopathogenesis of AD and effective drugs for AD treatment are still largely unsolved.The present review was mainly focused on the molecular mechanism of Aβ aggregation-related impairment and the pathways leading to tau hyperphosphorylation,based on which some promising therapeutic targets for AD were also proposed.
There is no effective drug to treat Alzheimer＇s disease （AD）, a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta （Aβ） may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors （NTFs）. Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.
Lian-Feng LinMin-Jing LiaoXiao-Yan XueWei ZhangLi YanLiang CaiXiao-Wen ZhouXing ZhouHuan-Min Luo
Objective To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schi-zandrin （Sch） against dexamethasone （Dex）-induced neurotoxicity in vivo and in vitro. Methods Cerebral cortical cells from neonatal Sprague-Dawley rats （within 24 hours after birth） were cultured for 9 days, and then treated with Dex （10 -4 , 10 -5 , 10 -6 or 10 -7 mol/L） for 24 h or pretreated with 10 -4 mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Schfor 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups： control [（intragastric （i.g.） vehicle for 42 days]; Dex group I （5 mg/kg·d -1 Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days）; Dex group II （Dex i.g. for 42 days）; Dex ＋ Sch （Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg·d -1 Sch i.g. for 14 days）. Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons. Results Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes. Conclusion Sch has neuroprotective effects against insults induced by glucocorticoid.
Xiao XuXing ZhouXiao-Wen ZhouZheng ZhangMin-Jing LiaoQi GaoHuan-Min Luo
