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SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease
Wu, Xiaoli; Kosaraju, Jayasankar; Zhou, Wei; Tam, Kin Yip
2018-03-15
Source PublicationNEUROPHARMACOLOGY
ISSN0028-3908
Volume131Pages:351-363
AbstractAlzheimer's disease (AD) is a progressive neurodegenerative dysfunction characterized by memory impairment and brings a heavy burden to old people both in developing and developed countries. Amyloid hypothesis reveals that aggregation and deposition of amyloid plaques are the cause of AD neurodegeneration. SLOH, a carbazole-based fluorophore, is reported to inhibit amyloid beta (A beta) aggregation in vitro. In the current study, we intended to evaluate the protective effect of SLOH in a triple transgenic AD mouse model (3xTg-AD). 3xTg-AD (10-month-old) were treated with SLOH (0.5, 1 and 2 mg kg(-1)) for one month via intraperitoneal injection. After treatment, cognitive function was assessed by Morris Water Maze (MWM) and Y-maze tasks. In addition, biochemical estimations were used to examine the degree of A beta deposition, tau hyperphosphorylation and neuroinflammation in the brains of 3xTg-AD mice. An in vitro study was conducted on human neuroblastoma (SH-SY5Y) cells to determine the activity of SLOH on tau and GSK-3 beta using western blot and immunofluorescence staining. One month treatment with SLOH significantly ameliorated memory impairments in 3xTg-AD mice in MWM and Y-maze tests. Moreover, SLOH treatment mitigated the level of amyloid plaques, tau hyperphosphorylation and neuroinflammation in the mouse brain. SLOH also reduced tau hyperphosphorylation and down regulated GSK-3 beta activity in A beta induced neurotoxic SH-SY5Y cells. The promising results in mitigating amyloid plaques, tau hyperphosphorylation, neuroinflammation and ameliorating cognitive deficits following one-month treatment suggest that SLOH could be a potential multi-target molecule for the AD treatment. (C) 2018 Elsevier Ltd. All rights reserved.
KeywordAmyloid beta Aggregation Alzheimer's disease 3xTg-AD Neuroprotection SH-SY5Y
DOI10.1016/j.neuropharm.2018.01.003
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology ; Pharmacology & Pharmacy
WOS SubjectNeurosciences ; Pharmacology & Pharmacy
WOS IDWOS:000427316000031
PublisherPERGAMON-ELSEVIER SCIENCE LTD
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
AffiliationUniv Macau, Fac Hlth Sci, Taipa, Macau, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Wu, Xiaoli,Kosaraju, Jayasankar,Zhou, Wei,et al. SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease[J]. NEUROPHARMACOLOGY,2018,131:351-363.
APA Wu, Xiaoli,Kosaraju, Jayasankar,Zhou, Wei,&Tam, Kin Yip.(2018).SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease.NEUROPHARMACOLOGY,131,351-363.
MLA Wu, Xiaoli,et al."SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease".NEUROPHARMACOLOGY 131(2018):351-363.
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