Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease
Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue...
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Elsevier
2016-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861316301190 |
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| author | Sha Liu Shuang-Qi Tang Heng-Jing Cui Sha Yin Ming Yin Hong Zhao Ling-Hua Meng Ze-Jian Wang Yang Lu |
| author_facet | Sha Liu Shuang-Qi Tang Heng-Jing Cui Sha Yin Ming Yin Hong Zhao Ling-Hua Meng Ze-Jian Wang Yang Lu |
| author_sort | Sha Liu |
| collection | DOAJ |
| description | Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)SWE/presenilin-1 (PS1)M146V/TauP301L mouse (3×Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms. NSTK could increase spontaneous locomotor activity in the open field and low anxiety-like behavior in the elevated plus maze, and improve the spatial memory deficits in the Morris water maze. The biochemical analysis suggested that NSTK could decrease Aβ42 deposition, abnormal tau aggregation, and the expressions of p-APP Thr668, PS1 and p-tau Ser202/Thr205 in the hippocampus of 3×Tg-AD mice. Consistently, NSTK could reduce the level of malondialdehyde, increase the activity of superoxide dismutase and catalase. Up-regulation of Bcl-2, and down-regulation of BAX, caspase-3 and inflammatory cytokines also occurred in the hippocampus of 3×Tg-AD mice after treatment with NSTK. Thus, NSTK could intervene in multiple pathological processes of AD and would be a drug candidate against AD. |
| first_indexed | 2024-12-11T04:17:23Z |
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| id | doaj.art-35ac7b73c3134111979e8e3fbe5f3430 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T04:17:23Z |
| publishDate | 2016-09-01 |
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| spelling | doaj.art-35ac7b73c3134111979e8e3fbe5f34302022-12-22T01:21:13ZengElsevierJournal of Pharmacological Sciences1347-86132016-09-011321929910.1016/j.jphs.2016.08.009Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's diseaseSha Liu0Shuang-Qi Tang1Heng-Jing Cui2Sha Yin3Ming Yin4Hong Zhao5Ling-Hua Meng6Ze-Jian Wang7Yang Lu8Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaInstitute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaInstitute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaInstitute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, ChinaInstitute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, ChinaInstitute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, ChinaRecently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)SWE/presenilin-1 (PS1)M146V/TauP301L mouse (3×Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms. NSTK could increase spontaneous locomotor activity in the open field and low anxiety-like behavior in the elevated plus maze, and improve the spatial memory deficits in the Morris water maze. The biochemical analysis suggested that NSTK could decrease Aβ42 deposition, abnormal tau aggregation, and the expressions of p-APP Thr668, PS1 and p-tau Ser202/Thr205 in the hippocampus of 3×Tg-AD mice. Consistently, NSTK could reduce the level of malondialdehyde, increase the activity of superoxide dismutase and catalase. Up-regulation of Bcl-2, and down-regulation of BAX, caspase-3 and inflammatory cytokines also occurred in the hippocampus of 3×Tg-AD mice after treatment with NSTK. Thus, NSTK could intervene in multiple pathological processes of AD and would be a drug candidate against AD.http://www.sciencedirect.com/science/article/pii/S1347861316301190Alzheimer's diseaseAPPSWE/PS1M146V/TauP301L mouse modelDipotassium N-stearoyltyrosinateAnimal behaviorNeuroprotection |
| spellingShingle | Sha Liu Shuang-Qi Tang Heng-Jing Cui Sha Yin Ming Yin Hong Zhao Ling-Hua Meng Ze-Jian Wang Yang Lu Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease Journal of Pharmacological Sciences Alzheimer's disease APPSWE/PS1M146V/TauP301L mouse model Dipotassium N-stearoyltyrosinate Animal behavior Neuroprotection |
| title | Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease |
| title_full | Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease |
| title_fullStr | Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease |
| title_full_unstemmed | Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease |
| title_short | Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease |
| title_sort | dipotassium n stearoyltyrosinate ameliorated pathological injuries in triple transgenic mouse model of alzheimer s disease |
| topic | Alzheimer's disease APPSWE/PS1M146V/TauP301L mouse model Dipotassium N-stearoyltyrosinate Animal behavior Neuroprotection |
| url | http://www.sciencedirect.com/science/article/pii/S1347861316301190 |
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