Cited by 166Inflammasome and immune disordersNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease

Pennisi, Manuela, Crupi, Rosalia, Di Paola, Rosanna, Ontario, Maria Laura, Bella, Rita, Calabrese, Edward J., Crea, Roberto, Cuzzocrea, Salvatore +1 more·2017·Journal of Neuroscience Research

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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Crossref · 10.1002/jnr.23986

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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
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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