PMID- 25024319
OWN - NLM
STAT- MEDLINE
DCOM- 20150825
LR  - 20181202
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 42
IP  - 3
DP  - 2014
TI  - Novel multipotent AChEI-CCB attenuates hyperhomocysteinemia-induced memory 
      deficits and Neuropathologies in rats.
PG  - 1029-39
LID - 10.3233/JAD-140597 [doi]
AB  - Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive 
      cause remains unclear and the therapeutic strategies have been elusive. 
      Combination therapy, as one of the promising treatments, has been studied for 
      years and may exert synergistic beneficial effects on AD through polytherapeutic 
      targets. In this study, we tested the effects of a synthesized juxtaposition 
      (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a 
      calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat 
      model, and found that SCR1693 remarkably improved the HHcy-induced memory 
      deficits and preserved dendrite morphologies as well as spine density by 
      upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, 
      SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple 
      AD-associated sites by regulating the activity of protein phosphatase-2A and 
      glycogen synthase kinase-3beta. Furthermore, SCR1693 was more effective than 
      individual administration of both donepezil and nilvadipine which were used as 
      AChEI and CCB, respectively, in the clinical practice. In conclusion, our data 
      suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a 
      promising therapeutic candidate for AD.
FAU - Xia, Yiyuan
AU  - Xia Y
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Liu, Rong
AU  - Liu R
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Chen, Rong
AU  - Chen R
AD  - Jiangsu Simovay Pharmaceutical Co., Ltd., Nanjing, China.
FAU - Tian, Qing
AU  - Tian Q
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Zeng, Kuan
AU  - Zeng K
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Hu, Jichang
AU  - Hu J
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Liu, Xinghua
AU  - Liu X
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Wang, Qun
AU  - Wang Q
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Wang, Peng
AU  - Wang P
AD  - Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China.
FAU - Wang, Xiao-Chuan
AU  - Wang XC
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Wang, Jian-Zhi
AU  - Wang JZ
AD  - Department of Pathophysiology, Key Laboratory of Education Ministry of China for 
      Neurological Disorders, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperidines)
RN  - 0 (SCR1693)
RN  - 0214FUT37J (nilvadipine)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 4VX7YNB537 (Tacrine)
RN  - 8SSC91326P (Donepezil)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Animals
MH  - *Brain Diseases/drug therapy/etiology/pathology
MH  - Calcium Channel Blockers/*therapeutic use
MH  - Cholinesterase Inhibitors/*therapeutic use
MH  - Disease Models, Animal
MH  - Donepezil
MH  - Drug Therapy, Combination
MH  - Hippocampus/drug effects/pathology/ultrastructure
MH  - Homocysteine/toxicity
MH  - Hyperhomocysteinemia/chemically induced/*complications
MH  - Indans/therapeutic use
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory Disorders/*drug therapy/*etiology
MH  - Nerve Tissue Proteins/metabolism
MH  - Nifedipine/analogs & derivatives/therapeutic use
MH  - Piperidines/therapeutic use
MH  - Prefrontal Cortex/drug effects/pathology/ultrastructure
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Silver Staining
MH  - Tacrine/analogs & derivatives/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - GSK-3beta
OT  - PP2A
OT  - SCR1693
OT  - hyperhomocysteinemia
OT  - tau
EDAT- 2014/07/16 06:00
MHDA- 2015/08/26 06:00
CRDT- 2014/07/16 06:00
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/08/26 06:00 [medline]
AID - H46626M11U204236 [pii]
AID - 10.3233/JAD-140597 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2014;42(3):1029-39. doi: 10.3233/JAD-140597.