Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca2+/CaMKII/CREB signaling pathway

Chen Chen; Di Xu; Zhong Hao Zhang; Shi Zheng Jia; Xian Chun Cao; Yu Bin Chen; Guo Li Song; Ricky M S WONG; Hung Wing Li

doi:10.1016/j.expneurol.2020.113210

Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca²⁺/CaMKII/CREB signaling pathway

Chen Chen, Di Xu, Zhong Hao Zhang, Shi Zheng Jia, Xian Chun Cao, Yu Bin Chen, Guo Li Song, Ricky M S WONG^*, Hung Wing Li

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca²⁺/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.

Original language	English
Article number	113210
Journal	Experimental Neurology
Volume	327
DOIs	https://doi.org/10.1016/j.expneurol.2020.113210
Publication status	Published - May 2020

Scopus Subject Areas

Neurology
Developmental Neuroscience

User-Defined Keywords

Alzheimer's disease
Aβ
Calcium pathway
Hyperphosphorylated tau
SLOH

Access to Document

10.1016/j.expneurol.2020.113210

Cite this

Chen, C., Xu, D., Zhang, Z. H., Jia, S. Z., Cao, X. C., Chen, Y. B., Song, G. L., WONG, R. M. S., & Li, H. W. (2020). Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca²⁺/CaMKII/CREB signaling pathway. Experimental Neurology, 327, [113210]. https://doi.org/10.1016/j.expneurol.2020.113210

@article{ce257c6cfaba4c5ba5646ca2359dcb74,

title = "Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca2+/CaMKII/CREB signaling pathway",

abstract = "Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca2+/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.",

keywords = "Alzheimer's disease, Aβ, Calcium pathway, Hyperphosphorylated tau, SLOH",

author = "Chen Chen and Di Xu and Zhang, {Zhong Hao} and Jia, {Shi Zheng} and Cao, {Xian Chun} and Chen, {Yu Bin} and Song, {Guo Li} and WONG, {Ricky M S} and Li, {Hung Wing}",

note = "Funding Information: This work was supported by Guangdong Natural Science Foundation (Nos. 2018B030336001, 2018A030310447), and Collaborative Research Fund of Hong Kong Research Grant Council (C2012-15G) and the National Natural Sciences Foundation of China (Nos. 21675135, 31800681). We are extremely thankful to Instrumental Analysis Center of Shenzhen University for excellent technical assistance. Funding Information: This work was supported by Guangdong Natural Science Foundation (Nos. 2018B030336001 , 2018A030310447 ), and Collaborative Research Fund of Hong Kong Research Grant Council ( C2012-15G ) and the National Natural Sciences Foundation of China (Nos. 21675135 , 31800681 ). We are extremely thankful to Instrumental Analysis Center of Shenzhen University for excellent technical assistance.",

year = "2020",

month = may,

doi = "10.1016/j.expneurol.2020.113210",

language = "English",

volume = "327",

journal = "Experimental Neurology",

issn = "0014-4886",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca2+/CaMKII/CREB signaling pathway

AU - Chen, Chen

AU - Xu, Di

AU - Zhang, Zhong Hao

AU - Jia, Shi Zheng

AU - Cao, Xian Chun

AU - Chen, Yu Bin

AU - Song, Guo Li

AU - WONG, Ricky M S

AU - Li, Hung Wing

N1 - Funding Information: This work was supported by Guangdong Natural Science Foundation (Nos. 2018B030336001, 2018A030310447), and Collaborative Research Fund of Hong Kong Research Grant Council (C2012-15G) and the National Natural Sciences Foundation of China (Nos. 21675135, 31800681). We are extremely thankful to Instrumental Analysis Center of Shenzhen University for excellent technical assistance. Funding Information: This work was supported by Guangdong Natural Science Foundation (Nos. 2018B030336001 , 2018A030310447 ), and Collaborative Research Fund of Hong Kong Research Grant Council ( C2012-15G ) and the National Natural Sciences Foundation of China (Nos. 21675135 , 31800681 ). We are extremely thankful to Instrumental Analysis Center of Shenzhen University for excellent technical assistance.

PY - 2020/5

Y1 - 2020/5

N2 - Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca2+/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.

AB - Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca2+/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.

KW - Alzheimer's disease

KW - Aβ

KW - Calcium pathway

KW - Hyperphosphorylated tau

KW - SLOH

UR - http://www.scopus.com/inward/record.url?scp=85078928070&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2020.113210

DO - 10.1016/j.expneurol.2020.113210

M3 - Article

C2 - 31987831

AN - SCOPUS:85078928070

SN - 0014-4886

VL - 327

JO - Experimental Neurology

JF - Experimental Neurology

M1 - 113210

ER -