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Abstract Title:

Rose Bengal inhibitsβ-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

Abstract Source:

Psychopharmacology (Berl). 2022 Oct 12. Epub 2022 Oct 12. PMID: 36221038

Abstract Author(s):

Chen-Ye Mou, Yan-Fei Xie, Jia-Xin Wei, Qi-Yao Wang, Jing-Yang Le, Yong-Jie Bao, Pan-Pan Zhang, Yue-Chun Mao, Xing-Han Huang, Han-Bo Pan, C Benjamin Naman, Lin Liu, Hong-Ze Liang, Xiang Wu, Jia Xu, Wei Cui

Article Affiliation:

Chen-Ye Mou

Abstract:

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents.

OBJECTIVES: The research aimed to investigate if and how RB could preventβ-amyloid (Aβ) oligomers-induced tau hyperphosphorylation in rodents.

METHODS AND RESULTS: RB was tested in vitro (0.3-1 μM) and prevented Aβ oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aβ oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3β (GSK3β) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3β and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation.

CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3β and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.

Study Type : In Vitro Study

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