| Title |
A novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improves Aβ25–35-impaired mouse cognitive function
|
|---|---|
| Published in |
Psychopharmacology, November 2015
|
| DOI | 10.1007/s00213-015-4133-5 |
| Pubmed ID | |
| Authors |
Zhengping Zhang, Rong Chen, Wenji An, Chunmei Wang, Gaoyong Liao, Xiaoliang Dong, Aijing Bi, Zhimin Yin, Lan Luo |
| Abstract |
The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy. We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Aβ25-35-injected mice, and the potential mechanisms. AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Aβ25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Aβ25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12. SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Aβ25-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Aβ25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Aβ25-35-induced signal cascade in neurons. All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 35 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 20% |
| Student > Bachelor | 4 | 11% |
| Other | 4 | 11% |
| Student > Doctoral Student | 3 | 9% |
| Student > Master | 3 | 9% |
| Other | 6 | 17% |
| Unknown | 8 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 7 | 20% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Nursing and Health Professions | 3 | 9% |
| Chemistry | 3 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Other | 5 | 14% |
| Unknown | 12 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 November 2015.
All research outputs
#3,200,780
of 22,832,057 outputs
Outputs from Psychopharmacology
#812
of 5,348 outputs
Outputs of similar age
#47,252
of 282,576 outputs
Outputs of similar age from Psychopharmacology
#8
of 56 outputs
Altmetric has tracked 22,832,057 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,348 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has done well, scoring higher than 84% of its peers.
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We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.