Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease
Abstract
Alzheimer disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline, neuropsychiatric symptoms, disability, caregiver burden, and premature death. It represents the most prevalent cause of dementia, and its incidence rates exponentially increase with increasing age. The number of Americans living with AD is rapidly increasing. An estimated 5.4 million Americans of all ages have AD in 2016. One in nine people aged 65 and older has AD, and by midcentury, someone in the United States will develop the disease every 33 sec. It is now accepted that neuroinflammation is a common feature of neurological disease. Inflammasomes, which are a multiprotein complex part of the innate immune system, induce inflammation in response to various stimuli, such as pathogens and stress. Inflammasomes activate proinflammatory caspases, such as caspase-1, leading to the activation of the proinflammatory cytokines interleukin (IL)-1b, IL-18, and IL-33, which promote neuroinflammation and brain pathologies. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing-3 (NLRP3) inflammasome is the best characterized in neurodegenerative diseases, in particular AD. Recent research suggests that NLRP3 could possibly be used in targeted therapies to alleviate neuroinflammation. Modulation of endogenous cellular defense mechanisms may be an innovative approach to therapeutic intervention in AD and other disorders associated with neuroinflammation and neurodegeneration. Herein, we introduce the hormetic dose-response concept and present possible mechanisms and applications to neuroprotection. We summarize the mechanisms involved in activation of the NLRP3 inflammasome and its role in neuroinflammation. We also address and propose the potential therapeutic utility of the nutritional antioxidants sulforaphane and hydroxytyrosol against particular signs and symptoms of AD. © 2016 Wiley Periodicals, Inc.
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Ferulic acid, caffeic acid, tyrosol, hydroxytyrosol, and vanillic acid have been evaluated as therapeutic agents in neuroinflammation diseases.
“Ferulic acid, CA, tyrosol, hydroxytyrosol, and vanillic acid have been evaluated as therapeutic agents in neuroinflammation diseases [160].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [160]
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- Authors
- Pennisi, M., Crupi, R., Di Paola, R., Ontario, M. L., Bella, R., Calabrese, E. J., Crea, R., Cuzzocrea, S., & Calabrese, V.
- Affiliations
- University of Catania (IT)
- University of Messina (IT)
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
- University of Massachusetts Amherst (US)
- CreAgri Incorporated Hayward California
- Corresponding author
- Calabrese, Vittorio
- ORCID
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2016-11-08
- Volume
- 95
- Issue
- 7
- Pages
- 1360-1372
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2555324658
- Cited by
- 157
- References
- 148
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 31 · 2021: 14 · 2020: 11 · 2019: 21 · 2018: 23 · 2017: 13
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, NLRP3 inflammasome, neuroinflammation, hormesis, antioxidants, sulforaphane, hydroxytyrosol, caspase-1, IL-1β, neuroprotection, neurodegeneration, innate immunity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Alzheimer Disease, Animals, Antioxidants, Humans, Inflammation, Inflammation Mediators, Inflammasomes, Hormesis
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