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Pharmacological Potential of Cilostazol for Alzheimer’s Disease

Alzheimer’s disease (AD), a slow progressive form of dementia, is clinically characterized by cognitive dysfunction and memory impairment and neuropathologically characterized by the accumulation of extracellular plaques containing amyloid β-protein (Aβ) and neurofibrillary tangles containing tau in...

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Autores principales: Ono, Kenjiro, Tsuji, Mayumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540873/
https://www.ncbi.nlm.nih.gov/pubmed/31191308
http://dx.doi.org/10.3389/fphar.2019.00559
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author Ono, Kenjiro
Tsuji, Mayumi
author_facet Ono, Kenjiro
Tsuji, Mayumi
author_sort Ono, Kenjiro
collection PubMed
description Alzheimer’s disease (AD), a slow progressive form of dementia, is clinically characterized by cognitive dysfunction and memory impairment and neuropathologically characterized by the accumulation of extracellular plaques containing amyloid β-protein (Aβ) and neurofibrillary tangles containing tau in the brain, with neuronal degeneration and high level of oxidative stress. The current treatments for AD, e.g., acetylcholinesterase inhibitors (AChEIs), have efficacies limited to symptom improvement. Although there are various approaches to the disease modifying therapies of AD, none of them can be used alone for actual treatment, and combination therapy may be needed for amelioration of the progression. There are reports that cilostazol (CSZ) suppressed cognitive decline progression in patients with mild cognitive impairment or stable AD receiving AChEIs. Previously, we showed that CSZ suppressed Aβ-induced neurotoxicity in SH-SY5Y cells via coincident inhibition of oxidative stress, as demonstrated by reduced activity of nicotinamide adenine dinucleotide phosphate oxidase, accumulation of reactive oxygen species, and signaling of mitogen-activated protein kinase. CSZ also rescued cognitive impairment and promoted soluble Aβ clearance in a mouse model of cerebral amyloid angiopathy. Mature Aβ fibrils have long been considered the primary neurodegenerative factors in AD; however, recent evidence indicates soluble oligomers to initiate the neuronal and synaptic dysfunction related to AD and other protein-misfolding diseases. Further underscoring the potential of CSZ for AD treatment, we recently described the inhibitory effects of CSZ on Aβ oligomerization and aggregation in vitro. In this review, we discuss the possibility of CSZ as a potential disease-modifying therapy for the prevention or delay of AD.
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spelling pubmed-65408732019-06-12 Pharmacological Potential of Cilostazol for Alzheimer’s Disease Ono, Kenjiro Tsuji, Mayumi Front Pharmacol Pharmacology Alzheimer’s disease (AD), a slow progressive form of dementia, is clinically characterized by cognitive dysfunction and memory impairment and neuropathologically characterized by the accumulation of extracellular plaques containing amyloid β-protein (Aβ) and neurofibrillary tangles containing tau in the brain, with neuronal degeneration and high level of oxidative stress. The current treatments for AD, e.g., acetylcholinesterase inhibitors (AChEIs), have efficacies limited to symptom improvement. Although there are various approaches to the disease modifying therapies of AD, none of them can be used alone for actual treatment, and combination therapy may be needed for amelioration of the progression. There are reports that cilostazol (CSZ) suppressed cognitive decline progression in patients with mild cognitive impairment or stable AD receiving AChEIs. Previously, we showed that CSZ suppressed Aβ-induced neurotoxicity in SH-SY5Y cells via coincident inhibition of oxidative stress, as demonstrated by reduced activity of nicotinamide adenine dinucleotide phosphate oxidase, accumulation of reactive oxygen species, and signaling of mitogen-activated protein kinase. CSZ also rescued cognitive impairment and promoted soluble Aβ clearance in a mouse model of cerebral amyloid angiopathy. Mature Aβ fibrils have long been considered the primary neurodegenerative factors in AD; however, recent evidence indicates soluble oligomers to initiate the neuronal and synaptic dysfunction related to AD and other protein-misfolding diseases. Further underscoring the potential of CSZ for AD treatment, we recently described the inhibitory effects of CSZ on Aβ oligomerization and aggregation in vitro. In this review, we discuss the possibility of CSZ as a potential disease-modifying therapy for the prevention or delay of AD. Frontiers Media S.A. 2019-05-22 /pmc/articles/PMC6540873/ /pubmed/31191308 http://dx.doi.org/10.3389/fphar.2019.00559 Text en Copyright © 2019 Ono and Tsuji. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Ono, Kenjiro
Tsuji, Mayumi
Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title_full Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title_fullStr Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title_full_unstemmed Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title_short Pharmacological Potential of Cilostazol for Alzheimer’s Disease
title_sort pharmacological potential of cilostazol for alzheimer’s disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540873/
https://www.ncbi.nlm.nih.gov/pubmed/31191308
http://dx.doi.org/10.3389/fphar.2019.00559
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