The DOI matches its Crossref record; 221 of the 222 references it cites were found in a registry or an index.
Flavonoids, cognition, and dementia: Actions, mechanisms, and potential therapeutic utility for Alzheimer disease
Abstract
There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.
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“This protein known as the BACE performs proteolysis by generating a soluble fragment in the extracellular space known as “soluble APPβ” and an additional fragment bound to the plasma membrane, CTFβ peptide that undergoes proteolysis yet again by γ-secretase to generate toxic neuropeptides Aβ with 40–43 amino acids, finally causing the amyloid plaques characteristic of AD [165,166,167].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [167]
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Items 201–221 of 221
Cerebral Correlates of the Progression Rate of the Cognitive Decline in Probable Alzheimer’s Disease
Nagahama, Y., Nabatame, H., Okina, T., Yamauchi, H., Narita, M., Fujimoto, N., Murakami, M., Fukuyama, H., & Matsuda, M. (2003) · European Neurology · doi:10.1159/000070851 · Cited by 70
Mandel, S. A., Reznichenko, L., Amit, T., & Youdim, M. B. H. (2003) · Neurotoxicity Research · doi:10.1007/bf03033171 · Cited by 70
Chan, Y., Hosoda, K., Chin-Ju, T. S. A. I., Yamamoto, S., & Ming-Fu, W. A. N. G. (2006) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.52.266 · Cited by 68
Bastianetto, S., Dumont, Y., Duranton, A., Vercauteren, F., Breton, L., & Quirion, R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012935 · Cited by 66
Wang, Z., Fernández‐Seara, M. A., Alsop, D. C., Liu, W., Flax, J. F., BENASICH, A. A., & Detre, J. A. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.045 · Cited by 63
Mao, T. K., de Water, J. V., Keen, C. L., Schmitz, H. H., & Gershwin, M. E. (2002) · Journal of Medicinal Food · doi:10.1089/109662002753723188 · Cited by 61
Howes, J. B., Bray, K., Lorenz, L., Smerdely, P., & Howes, L. G. (2004) · Climacteric · doi:10.1080/13697130310001651490 · Cited by 57
Pan, Y., Anthony, M. S., & Clarkson, T. B. (1999) · Experimental Biology and Medicine · doi:10.3181/00379727-221-44393 · Cited by 57
Panneerselvam, M., Tsutsumi, Y. M., Bonds, J. A., Horikawa, Y. T., Saldana, M., Dalton, N. D., Head, B. P., Patel, P. M., Roth, D. M., & Patel, H. H. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00073.2010 · Cited by 54
Shif, O. A., Gillette, K., Damkaoutis, C. M., Carrano, C., Robbins, S. J., & Hoffman, J. R. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.04.003 · Cited by 51
Incani, A., Deiana, M., Corona, G., Vafeiadou, K., Vauzour, D., Dessì, M., & Spencer, J. P. E. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200900098 · Cited by 50
Fernández, S. P., Mewett, K. N., Hanrahan, J. R., Chebib, M., & Johnston, G. A. R. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.069 · Cited by 47
Inhibition of the formation of the neurotoxin 5-S-cysteinyl-dopamine by polyphenols
Vauzour, D., Vafeiadou, K., & Spencer, J. P. E. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.153 · Cited by 42
Do flavan-3-ols from green tea reach the human brain?
Zini, A., Rio, D. D., Stewart, A. J., Mandrioli, J., Merelli, E., Sola, P., Nichelli, P., Serafini, M., Brighenti, F., Edwards, C. A., et al. (2006) · Nutritional Neuroscience · doi:10.1080/10284150600637739 · Cited by 39
Pasinetti, G. M., Ksiȩżak-Reding, H., Santa‐María, I., Wang, J., & Ho, L. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06875.x · Cited by 38
Llorens, F., Garcia, L., Itarte, E., & Gómez, N. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03252-5 · Cited by 38
Ginkgo biloba promotes short-term retention of spatial memory in rats
Hoffman, J. R., Donato, A., & Robbins, S. J. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2003.12.006 · Cited by 36
Cocoa Flavanols, Cerebral Blood Flow, Cognition, and Health: Going Forward
Dinges, D. F. (2006) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200606001-00019 · Cited by 33
Lee, B., Choi, S.-H., Shin, T., Pyo, M. K., Hwang, S., Kim, B., Lee, S., Lee, J., Kim, H., Park, H.-Y., et al. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0117-9 · Cited by 30
Effects of quercetin on α9α10 nicotinic acetylcholine receptor-mediated ion currents.
Lee, B., Choi, S.-H., Shin, T.-J., Pyo, M., Hwang, S., Lee, S.-M., Paik, H., Kim, H., & Nah, S. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.079 · Cited by 27
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Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects
Rahman, M. M., Rahaman, M. S., Islam, M. R., Rahman, F., Mithi, F. M., Alqahtani, T., Almikhlafi, M. A., Alghamdi, S. Q., Alruwaili, A. S., Hossain, M. S., et al. (2021) · Molecules · doi:10.3390/molecules27010233 · Cited by 945
Flavones: An important scaffold for medicinal chemistry
Singh, M., Kaur, M., & Silakari, O. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.07.013 · Cited by 551
Vauzour, D. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/914273 · Cited by 449
Astrocyte Heterogeneity: Impact to Brain Aging and Disease
Matias, I., Morgado, J., & Gomes, F. C. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00059 · Cited by 387
Ayaz, M., Sadiq, A., Junaid, M., Ullah, F., Ovais, M., Ullah, I., Ahmed, J., & Shahid, M. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00155 · Cited by 320
Metadata
- Authors
- Williams, R. J., & Spencer, J. P. E.
- Affiliations
- University of Bath (GB)
- University of Reading (GB)
- Corresponding author
- Spencer, Jeremy P.E.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 52
- Issue
- 1
- Pages
- 35-45
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2000424893
- Cited by
- 448
- References
- 222
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 28 · 2023: 16 · 2022: 36 · 2021: 34 · 2020: 36 · 2019: 38 · 2018: 34 · 2017: 42 · 2016: 34 · 2015: 37 · 2014: 36 · 2013: 33 · 2012: 15
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Society
- Biotechnology and Biological Sciences Research Council (BB/G005702/1, BB/E023185/1, BB/F008953/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- flavonoids, Alzheimer's disease, dementia, flavonoid-rich foods, green tea, blueberry, Theobroma cacao, flavonoid metabolites, ERK signaling, PI3K/Akt signaling, neuroprotection, neurogenesis, hippocampus, cerebral blood flow, neuronal apoptosis, oxidative stress, neuroinflammation, amyloid-beta aggregation, APP processing, BACE1, ADAM10, synaptic connectivity, cognitive function, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cognition, Enzyme Activation, Flavonoids, Humans, Neurons, Signal Transduction, Gene Expression, Amyloid beta-Peptides, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Mice, Rats, Amyloid Precursor Protein Secretases, Neurogenesis
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