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 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/TauP301Lmouse (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 Aβ42deposition, 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.
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
Sha
S
Liu
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
Shuang-Qi
SQ
Tang
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
Heng-Jing
HJ
Cui
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
Sha
S
Yin
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, China.
Ming
M
Yin
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, China.
Hong
H
Zhao
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
Ling-Hua
LH
Meng
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, China. Electronic address: wangzejian@sjtu.edu.cn.
Ze-Jian
ZJ
Wang
Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China. Electronic address: luyangssmu@163.com.
Yang
Y
Lu
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C494827:Bax protein, mouse; D016207:Cytokines; D018696:Neuroprotective Agents; D053764:Presenilin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016875:tau Proteins; D014443:Tyrosine; C087584:N-stearoyltyrosine; D053148:Caspase 3
APP(SWE)/PS1(M146V)/Tau(P301L) mouse model; Alzheimer's disease; Animal behavior; Dipotassium N-stearoyltyrosinate; Neuroprotection