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It is widely recognized that Alzheimer’s disease (AD) has a complicate link to renin-angiotensin system (RAS). It is known that cerebrovascular disease has some connections with AD, but most of the studies are still conducted in parallel or independently. Although previous research came up with large number of hypotheses about the pathogenesis of AD, it does not include the mechanism of RAS-related regulation of AD. It has been found that many components of RAS have been changed in AD. For example, the multifunctional and high-efficiency vasoconstrictor Ang II and Ang III with similar effects are changed under the action of other RAS signal peptides; these signal peptides are believed to help improve nerve injury and cognitive function. These changes may lead to neuropathological changes of AD, and progressive defects of cognitive function, which are association with some hypotheses of AD. The role of RAS in AD gradually attracts our attention, and RAS deserved to be considered carefully in the pathogenesis of AD. This review discusses the mechanisms of RAS participating in the three current hypotheses of AD: neuroinflammation, oxidative stress and amyloid-β protein (Aβ) hypothesis, as well as the drugs that regulate RAS systems already in clinical or in clinical trials. It further demonstrates the importance of RAS in the pathogenesis of AD, not only because of its multiple aspects of participation, which may be accidental, but also because of the availability of RAS drugs, which can be reused as therapies of AD.

Objective To investigate the neuroprotective effect of chrysophanol (CHR) on PC12 treated with Aβ 25-35 , and the involved mechanism. Methods After the establishment of an AD cell model induced by Aβ 25-35 , the cell survival rate was detected by MTT, cell apoptosis was assayed by Hoechst 33342 staining, mRNA expressions of calmodulin (CaM), calcium/calmodulin-dependent protein kinase kinase (CaMKK), calcium/calmodulin-dependent protein kinase IV (CaMKIV) and tau (MAPT; commonly known as tau) were determined by qRT-PCR, and protein levels of CaM, CaMKK, CaMKIV, phospho-CaMKIV (p-CaMKIV), tau and phospho-tau (p-tau) were detected by Western blot analysis. Results When pretreated with CHR before exposure to Aβ 25-35 , PC12 cells showed that increased cell viability and reduced apoptosis. The qRT-PCR results indicated that the deposition of Aβ 25-35 triggers a decrease in levels of CaM, CaMKK, CaMKIV, and tau in PC12 cells. In addition, Western blot results also suggested that Aβ 25-35 decreases the protein expression of CaM, CaMKK, CaMKIV, p-CaMKIV, and the ratio of p-tau to tau in PC12 cells. However, the above effects were significantly alleviated after the treatment of CHR. Conclusion CHR plays a neuroprotective role in AD though decreasing the protein level of CaM-CaMKK-CaMKIV and the expression of p-tau downstream.

Background Huangdi Anxiao (HDAX) is mainly used to treat diabetes and its complications for many years and has a remarkable curative effect. However, the improvement effect of HDAX in the diabetic cognitive dysfunction (DCD) model and the related mechanism is not clear. This study was aimed to explore the neuroprotective effects of HDAX and its possible mechanisms in DCD. Methods A DCD cell model was established by high glucose-induced PC12 cells, and the effect of HDAX on the cell viability was examined by MTT. Additionally, the expression of relevant genes and proteins in the apoptosis pathway of endoplasmic reticulum (ER) stress was detected. Results The results showed that HDAX increased cell viability, reduced GRP78, CHOP, Bax, procaspase-12, procaspase-9, procaspase-3 mRNA levels and GRP78, CHOP, Bax, Caspase-12, Caspase-9, Caspase-3 protein expressions, and decreased Bcl-2 mRNA level and protein expression. Conclusions These results suggested that HDAX had neuroprotective effects in the DCD cell model, which may be associated with the inhibition of the apoptosis pathway of ER stress.