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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 X.; Kosaraju J.; Zhou W.; Tam K.Y.
2017-03-15
Source PublicationACS Chemical Neuroscience
ISSN19487193
Volume8Issue:3Pages:676-685
Abstract

Amyloid β (Aβ) 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 Aβ aggregation is supposed to offer a neuroprotective effect to ameliorate AD. A previous report has shown that SLM, a carbazole-based fluorophore, binds to Aβ to inhibit the aggregation. However, it is not entirely clear whether the inhibition of Aβ aggregation alone would lead to the anticipated neuroprotective effects. In the current study, we intended to examine the protective action of SLM against Aβ-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 Aβ42 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 Aβ40 and Aβ42 levels and reduced tau phosphorylation, glycogen synthase kinase-3β activity, and neuro-inflammation. From our observations, SLM shows neuroprotection in SH-SY5Y cells against Aβ42 and also in 3xTg-AD mouse model by mitigating the pathological features and behavioral impairments.

Keyword3xtg-ad Aggregation Alzheimer’s Disease Amyloid β Neuroprotection Sh-sy5y Slm
DOIhttp://doi.org/10.1021/acschemneuro.6b00388
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
WOS IDWOS:000396807900027
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
AffiliationUniversidade de Macau
Recommended Citation
GB/T 7714
Wu X.,Kosaraju J.,Zhou W.,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 X.,Kosaraju J.,Zhou W.,&Tam K.Y..(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 X.,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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