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Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease
Wu, Xiaoli; Kosaraju, Jayasankar; Zhou, Wei; Tam, Kin Yip
2017-03
Source PublicationACS CHEMICAL NEUROSCIENCE
ISSN1948-7193
Volume8Issue:3Pages:676-685
AbstractAmyloid beta (A beta) peptide aggregating to form a neurotoxic plaque, leading to cognitive deficits, is believed to be one of the plausible mechanisms for Alzheimer's disease (AD). Inhibiting A beta aggregation is supposed to offer a neuroprotective effect to ameliorate AD. A previous report has shown that SLM, a carbazole-based fluorophore, binds to A beta to inhibit the aggregation. However, it is not entirely clear whether the inhibition of A beta aggregation alone would lead to the anticipated neuroprotective effects. In the current study, we intended to examine the protective action of SLM against A beta-induced neurotoxicity in vitro and to evaluate if SLM can decrease the cognitive and behavioral deficits observed in triple transgenic AD mouse model (3xTg-AD). In the in vitro study, neurotoxicity induced by A beta 42 in human neuroblastoma (SH-SY5Y) cells was found to be reduced through the treatment with SLM. In the in vivo study, following one month SLM intraperitoneal injection (1, 2, and 4 mg/kg), 3xTg-AD mice were tested on Morris water maze (MWM) and Y-maze for their cognitive ability and sacrificed for biochemical estimations. Results show that SLM treatment improved the learning and memory ability in 3xTg-AD mice in MWM and Y-maze tasks. SLM also mitigated the amyloid burden by decreasing brain A beta 40 and A beta 42 levels and reduced tau phosphorylation, glycogen synthase kinase-beta activity, and neuroinflammation. From our observations, SLM shows neuroprotection in SH-SY5Y cells against A beta 42 and also in 3xTg-AD mouse model by mitigating the pathological features and behavioral impairments.
KeywordAmyloid beta aggregation Alzheimer's disease SLM 3xTg-AD neuroprotection SH-SY5Y
DOI10.1021/acschemneuro.6b00388
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
WOS IDWOS:000396807900027
PublisherAMER CHEMICAL SOC
Fulltext Access
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationUniv Macau, Drug Dev Core, Fac Hlth Sci, Taipa, Madhya Pradesh, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Wu, Xiaoli,Kosaraju, Jayasankar,Zhou, Wei,et al. Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease[J]. ACS CHEMICAL NEUROSCIENCE,2017,8(3):676-685.
APA Wu, Xiaoli,Kosaraju, Jayasankar,Zhou, Wei,&Tam, Kin Yip.(2017).Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease.ACS CHEMICAL NEUROSCIENCE,8(3),676-685.
MLA Wu, Xiaoli,et al."Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease".ACS CHEMICAL NEUROSCIENCE 8.3(2017):676-685.
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