ArticleThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2020
Combination therapy with cilostazol, aripiprazole, and donepezil protects neuronal cells from β-amyloid neurotoxicity through synergistically enhanced SIRT1 expression.
Article in The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 12 citations in OpenAlex.
- sc4D: spatio-temporal single-cell transcriptomics analysis through embedded optimal transport identifies joint glial response to Alzheimer's disease pathology.bioRxiv : the preprint server for biology · 2025Article
- The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.Molecular neurobiology · 2024Review
- Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3Advances in pharmacological and pharmaceutical sciences · 2024Article
- Therapeutic Effects of Aripiprazole in the 5xFAD Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2021Article
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6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and a7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ
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