title: Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease.
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.
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Jayasankar
authors.initials: J
authors.lastname: Kosaraju
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Kin Yip
authors.identifier: 0000-0001-5507-8524
authors.initials: KY
authors.lastname: Tam
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry* / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D058225:Plaque, Amyloid / Q000209:etiology / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002227:Carbazoles; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; C041514:carbazole
keywords: 3xTg-AD; Alzheimer’s disease; Amyloid β; SH-SY5Y; SLM; aggregation; neuroprotection