摘要
OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated to effectively combat this devastating disease. Traditional Chinese medicine(TCM) has been widely used for treatment of dementia, and thus the advantages of the potential therapeutic features of TCM treatment and associated mechanisms should be well taken. The Amnesia Remedy Formula(ARF) was invented by one of the most influential Master of TCM SUN Si-miao, who lived for about 100 year old. The aim of this research is to characterize the time course changes of the cognitive behaviors post a ARF, and the mechanism underlying the effects, focusing on PKA-centered signaling for both enhancement of neural plasticity and clearance of the phosphorylated Tau. RESULTS We tested the efficacy of ARF on two animal models of AD, and examine the central role of PKA signaling in the enhancement of neural plasticity via PKA/CREB/BDNF pathway as well as clearance of toxic p Tau via PKA/GSK3β/p Tau pathway. In the scopolamine model, ARF effectively reversed the memory in Morris water maze(MWM) test, with some features superior to anti-AD drug donepezil. In a battery test of MWM, novel object recognition or T maze in 5-month-old senescenceaccelerated mouse prone 8(SAMP8) strain mice, two weeks of administration of ARF showed overall better improvement in memory loss than donepezil, and the effect lasted for at least 1 week after termination of administration of the formula. ARF increased expression of PKA/CREB/BDNF and synaptic proteins PSD95 expression, as well as enhanced Ser9 phosphorylation of GSK3β, thus reduced p Tau in the hippocampus. Blockade of PKA signaling blunted the anti-AD-like effect of ARF, with reversal of CREB/BDNF signaling. Transcriptomic analysis indicated some changes of novel molecules along this pathway may be part of the pathological and therapeutic mechanism, which warrants further investigation. CONCLUSION ARF may display some advantageous features in treating AD with early onset, via multi-targeted manner including enhancement of neural plasticity and reduction in Tau toxicity.
OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated to effectively combat this devastating disease. Traditional Chinese medicine(TCM) has been widely used for treatment of dementia, and thus the advantages of the potential therapeutic features of TCM treatment and associated mechanisms should be well taken. The Amnesia Remedy Formula(ARF) was invented by one of the most influential Master of TCM SUN Si-miao, who lived for about 100 year old. The aim of this research is to characterize the time course changes of the cognitive behaviors post a ARF, and the mechanism underlying the effects, focusing on PKA-centered signaling for both enhancement of neural plasticity and clearance of the phosphorylated Tau. RESULTS We tested the efficacy of ARF on two animal models of AD, and examine the central role of PKA signaling in the enhancement of neural plasticity via PKA/CREB/BDNF pathway as well as clearance of toxic p Tau via PKA/GSK3β/p Tau pathway. In the scopolamine model, ARF effectively reversed the memory in Morris water maze(MWM) test, with some features superior to anti-AD drug donepezil. In a battery test of MWM, novel object recognition or T maze in 5-month-old senescenceaccelerated mouse prone 8(SAMP8) strain mice, two weeks of administration of ARF showed overall better improvement in memory loss than donepezil, and the effect lasted for at least 1 week after termination of administration of the formula. ARF increased expression of PKA/CREB/BDNF and synaptic proteins PSD95 expression, as well as enhanced Ser9 phosphorylation of GSK3β, thus reduced p Tau in the hippocampus. Blockade of PKA signaling blunted the anti-AD-like effect of ARF, with reversal of CREB/BDNF signaling. Transcriptomic analysis indicated some changes of novel molecules along this pathway may be part of the pathological and therapeutic mechanism, which warrants further investigation. CONCLUSION ARF may display some advantageous features in treating AD with early onset, via multi-targeted manner including enhancement of neural plasticity and reduction in Tau toxicity.
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第6期405-405,共1页
Chinese Journal of Pharmacology and Toxicology
