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Cited by 307Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesMedicinal Plants and Neuroprotection

The DOI matches its Crossref record; 164 of the 164 references it cites were found in a registry or an index.

Management of oxidative stress and other pathologies in Alzheimer’s disease

Open access
Simunkova, Miriama, Alwasel, Saleh H., Alhazza, Ibrahim M., Jomova, Klaudia, Kollar, Vojtech, Rusko, Miroslav, Valko, Marian·2019·Archives of Toxicology
DOI 10.1007/s00204-019-02538-y
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Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, characterized by the formation, aggregation and accumulation of amyloid beta, perturbed metal (copper, iron and zinc) homeostasis, metal-induced oxidative stress, neuroinflammation, aberrant activity of acetylcholinesterase (AChE) and other pathologies. The aim of this review is to discuss the current therapies based on the "combination-drugs-multitargets" strategy to target multiple pathologies to block the progression of pathogenesis of AD. In addition to cholinergic and amyloid targets, a significant effort is focused on targeting the metal-induced oxidative stress component of the disease. The main focus of research is based on modifications of existing drugs with specific biological activity. Tacrine was the first AChE inhibitor to be introduced into clinical practice and has been frequently used for the design of multitarget-directed ligands. A number of hybrid compounds containing tacrine and structural moieties derived from natural sources such as flavonoids [quercetin, rutin, coumarin, gallamine, resveratrol, scutellarin, anisidine, hesperetin, (-)-epicatechin] and other molecules (melatonin, trolox) have also been applied to function as multitarget-directed ligands. Most of these hybrids are potent inhibitors of AChE and butyrylcholinesterase and also of amyloid-beta aggregation. In addition, the antioxidant functionality, represented by coumarins, melatonin and other antioxidant molecules reduces the level of oxidative stress via ROS-scavenging mechanisms, as well as via chelation of redox-active Cu and Fe, thus suppressing the formation of ROS via the Fenton reaction. Various medicinal plants are under investigation for their ability to ameliorate symptoms of AD. The therapeutic potency of huperzine A and B, ginseng, curcumin and other compounds is manifested predominantly by the inhibitory action toward AChE, antioxidant or radical-scavenging and redox metal-chelating activity, inhibition of amyloid-beta aggregation and tau-protein hyperphosphorylation and antiinflammatory activity. Flavonoids not only function as antioxidants and metal-chelating agents, but also interact with protein kinase and lipid kinase signaling pathways, and others involving mitogen-activated protein kinase, NF-kappaB and tyrosine kinase. Among the most promising group of substances with potential activity against AD are the flavonoids, including myricetin, morin, rutin, quercetin, fisetin, kaempferol, apigenin and glycitein, which have been shown, in vitro, to possess antiamyloidogenic and fibril-destabilization activity, as well as being able to act as metal chelators and to suppressing oxidative stress. In terms of the clinical use of multifunctional hybrids, herbal drugs or flavonoids against AD, some remaining challenges are to establish the ideal dose to develop effective formulations to preserve bioavailability and to determine the stage when they should be administered. If the onset of the disease could be delayed by a decade, the number of AD victims would be significantly reduced.

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  1. Li P, Lapcik L (2018) The research of functional ingredients from corn silk. Chem Listy 112:93–97
  2. Ma X, Wu L, Zhao H, Zeng D, Bai S (2014) Research progress of the Chinese medicine and herb prevention effect of the Alzheimer’s disease. Hunan Chin Tradit Med 11:177–179

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Metadata

Authors
Simunkova, M., Alwasel, S. H., Alhazza, I. M., Jomova, K., Kollar, V., Rusko, M., & Valko, M.
Affiliations
  • King Saud University (SA)
  • Slovak University of Technology in Bratislava (SK)
ORCID
Venue
Archives of Toxicology
Publisher
Springer Science and Business Media LLC
Published
2019-08-22
Volume
93
Issue
9
Pages
2491-2513
ISSN
  • 0340-5761 (ISSN-L)
  • 1432-0738
DOI
10.1007/s00204-019-02538-y
OpenAlex
W2969291614
Cited by
303
References
164
Citations by year
2026: 31 · 2025: 50 · 2024: 43 · 2023: 56 · 2022: 55 · 2021: 34 · 2020: 29 · 2019: 4
FWCI
3.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Archives of Toxicology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR (APVV-15-0079, 1/0686/17)
  • DSF Program
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords
Alzheimer's disease, oxidative stress, acetylcholinesterase inhibitors, amyloid-beta aggregation, flavonoids, metal-induced oxidative stress, neuroinflammation, tau hyperphosphorylation, huperzine A, curcumin, ginseng, medicinal plants, antioxidant activity, redox-active metals
MeSH terms
Acetylcholinesterase, Alzheimer Disease, Antioxidants, Butyrylcholinesterase, Chelating Agents, Cholinesterase Inhibitors, Copper, Humans, Iron, Amyloid beta-Peptides, Oxidative Stress, Plant Preparations

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