Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive neuronal loss and cognitive decline. Oligomeric amyloid β (oAβ) is involved in the pathogenesis of AD by affecting synaptic plasticity and inhibiting long-term potentiation. Although several lines of evidence suggests that microglia, the resident immune cells in the central nervous system (CNS), are neurotoxic in the development of AD, the mechanism whether or how oAβ induces microglial neurotoxicity remains unknown. Here, we show that oAβ promotes the processing of pro-interleukin (IL)-1β into mature IL-1β in microglia, which then enhances microglial neurotoxicity. The processing is induced by an increase in activity of caspase-1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3) via mitochondrial reactive oxygen species (ROS) and partially via NADPH oxidase-induced ROS. The caspase-1 inhibitor Z-YVAD-FMK inhibits the processing of IL-1β, and attenuates microglial neurotoxicity. Our results indicate that microglia can be activated by oAβ to induce neuroinflammation through processing of IL-1β, a pro-inflammatory cytokine, in AD.
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Halle et al. found that fibrillar Aβ can induce secretion of IL-1β which depends on the presence of NLRP3.
“Halle et al. found that fibrillar Aβ can induce the secretion of IL-1β which depends on the presence of NLRP3.352,353”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [353]
Oligomeric Aβ (oAβ) can activate the NLRP3 inflammasome and induce IL-1β secretion in LPS-primed microglia.
“Oligomeric Aβ (oAβ) also can activate the NLRP3 inflammasome and induce IL-1β secretion in LPS-primed microglia, but this effect was not dependent on oAβ phagocytosis and release of cathepsin B from damaged lysosomes.”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [79]
The effect of oAβ on NLRP3 inflammasome activation and IL-1β secretion in LPS-primed microglia is not dependent on oAβ phagocytosis and release of cathepsin B from damaged lysosomes.
“Oligomeric Aβ (oAβ) also can activate the NLRP3 inflammasome and induce IL-1β secretion in LPS-primed microglia, but this effect was not dependent on oAβ phagocytosis and release of cathepsin B from damaged lysosomes.”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [79]
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References 55 · Cited by 232
Research works printed but not linked: 39
- Walsh DM Teplow DB Alzheimer's disease and the amyloid beta-protein Prog Mol Biol Transl Sci 2012 107 101 124 22482449
- Selkoe D Mandelkow E Holtzman D Deciphering Alzheimer disease Cold Spring Harb Perspect Med 2012 2 a011460 22315723 PMC3253026
- Mawuenyega KG Sigurdson W Ovod V Munsell L Kasten T Morris JC Decreased clearance of CNS beta-amyloid in Alzheimer's disease Science 2010 330 1774 21148344 PMC3073454
- Gandy S The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease J Clin Invest 2005 115 1121 1129 15864339 PMC1087184
- Klug GM Losic D Subasinghe SS Aguilar MI Martin LL Small DH Beta-amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH Eur J Biochem 2003 270 4282 4293 14622293
- Mastrangelo IA Ahmed M Sato T Liu W Wang C Hough P High-resolution atomic force microscopy of soluble Abeta42 oligomers J Mol Biol 2006 358 106 119 16499926
- Lue LF Kuo YM Roher AE Brachova L Shen Y Sue L Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease Am J Pathol 1999 155 853 862 10487842 PMC1866907
- Santos AN Ewers M Minthon L Simm A Silber RE Blennow K Amyloid-beta oligomers in cerebrospinal fluid are associated with cognitive decline in patients with Alzheimer's disease J Alzheimers Dis 2012 29 171 176 22214781
- Cameron B Landreth GE Inflammation, microglia, and Alzheimer's disease Neurobiol Dis 2010 37 503 509 19833208 PMC2823849
- Heneka MT Sastre M Dumitrescu-Ozimek L Dewachter I Walter J Klockgether T Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice J Neuroinflammation 2005 2 22 16212664 PMC1274341
- Rodriguez JJ Witton J Olabarria M Noristani HN Verkhratsky A Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease Cell Death Dis 2010 1 e1 21364611 PMC3032511
- Ferretti MT Allard S Partridge V Ducatenzeiler A Cuello AC Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology J Neuroinflammation 2012 9 62 22472085 PMC3352127
- Weber A Wasiliew P Kracht M Interleukin-1beta (IL-1beta) processing pathway Sci Signal 2010 3cm2. 20086236
- Netea MG Simon A van de Veerdonk F Kullberg BJ Van der Meer JW Joosten LA IL-1beta processing in host defense: beyond the inflammasomes PLoS Pathog 2010 6 e1000661 20195505 PMC2829053
- Stutz A Golenbock DT Latz E Inflammasomes: too big to miss J Clin Invest 2009 119 3502 3511 19955661 PMC2786809
- Fernandes-Alnemri T Wu J Yu JW Datta P Miller B Jankowski W The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation Cell Death Differ 2007 14 1590 1604 17599095 PMC3345951
- Salminen A Ojala J Suuronen T Kaarniranta K Kauppinen A Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer's pathology J Cell Mol Med 2008 12 2255 2262 18793350 PMC4514104
- Terada K Yamada J Hayashi Y Wu Z Uchiyama Y Peters C Involvement of cathepsin B in the processing and secretion of interleukin-1beta in chromogranin A-stimulated microglia Glia 2010 58 114 124 19544382
- Dostert C Guarda G Romero JF Menu P Gross O Tardivel A Malarial hemozoin is a Nalp3 inflammasome activating danger signal PLoS One 2009 4 e6510 19652710 PMC2714977
- Bauernfeind F Bartok E Rieger A Franchi L Nunez G Hornung V Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome J Immunol 2011 187 613 617 21677136 PMC3131480
- Parvathy S Rajadas J Ryan H Vaziri S Anderson L Murphy GM Jr Abeta peptide conformation determines uptake and interleukin-1alpha expression by primary microglial cells Neurobiol Aging 2009 30 1792 1804 18339452
- Maezawa I Zimin PI Wulff H Jin LW Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity J Biol Chem 2011 286 3693 3706 20971854 PMC3030372
- Lindberg C Selenica ML Westlind-Danielsson A Schultzberg M Beta-amyloid protein structure determines the nature of cytokine release from rat microglia J Mol Neurosci 2005 27 1 12 16055942
- Qin B Cartier L Dubois-Dauphin M Li B Serrander L Krause KH A key role for the microglial NADPH oxidase in APP-dependent killing of neurons Neurobiol Aging 2006 27 1577 1587 16260066
- Wilkinson BL Landreth GE The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer's disease J Neuroinflammation 2006 3 30 17094809 PMC1637099
- Abramov AY Canevari L Duchen MR Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase J Neurosci 2004 24 565 575 14724257 PMC6729998
- Reddy PH Beal MF Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease Trends Mol Med 2008 14 45 53 18218341 PMC3107703
- Sesti F Liu S Cai SQ Oxidation of potassium channels by ROS: a general mechanism of aging and neurodegeneration Trends Cell Biol 2010 20 45 51 19850480
- Lashuel HA Hartley D Petre BM Walz T Lansbury PT Jr Neurodegenerative disease: amyloid pores from pathogenic mutations Nature 2002 418 291 12124613
- Yu SP Farhangrazi ZS Ying HS Yeh CH Choi DW Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death Neurobiol Dis 1998 5 81 88 9746905
- Pan XD Zhu YG Lin N Zhang J Ye QY Huang HP Microglial phagocytosis induced by fibrillar beta-amyloid is attenuated by oligomeric beta-amyloid: implications for Alzheimer's disease Mol Neurodegener 2011 6 45 21718498 PMC3149591
- Moore AH Wu M Shaftel SS Graham KA O'Banion MK Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory Neuroscience 2009 164 1484 1495 19744544 PMC2783232
- Vereker E O'Donnell E Lynch MA The inhibitory effect of interleukin-1beta on long-term potentiation is coupled with increased activity of stress-activated protein kinases J Neurosci 2000 20 6811 6819 10995825 PMC6772832
- Li Y Liu L Barger SW Griffin WS Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway J Neurosci 2003 23 1605 1611 12629164 PMC3833596
- Ghosh S Wu MD Shaftel SS Kyrkanides S LaFerla FM Olschowka JA Sustained interleukin-1beta overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer's mouse model J Neurosci 2013 33 5053 5064 23486975 PMC3637949
- Griffin WS Stanley LC Ling C White L MacLeod V Perrot LJ Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease Proc Natl Acad Sci USA 1989 86 7611 7615 2529544 PMC298116
- Craft JM Watterson DM Hirsch E Van Eldik LJ Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human beta-amyloid J Neuroinflammation 2005 2 15 15967035 PMC1190207
- Suzumura A Sawada M Takayanagi T Production of interleukin-12 and expression of its receptors by murine microglia Brain Res 1998 787 139 142 9518583
- Parajuli B Sonobe Y Kawanokuchi J Doi Y Noda M Takeuchi H GM-CSF increases LPS-induced production of proinflammatory mediators via upregulation of TLR4 and CD14 in murine microglia J Neuroinflammation 2012 9 268 23234315 PMC3565988
- Authors
- Parajuli, B., Sonobe, Y., Horiuchi, H., Takeuchi, H., Mizuno, T., & Suzumura, A.
- Affiliations
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Corresponding author
- Mizuno, T
- Venue
- Cell Death & Disease
- Published
- 2013-12-19
- Volume
- 4
- Issue
- 12
- Pages
- e975-e975
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3877570
- OpenAlex
- W2074472141
- Cited by
- 232
- References
- 55
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 15 · 2023: 19 · 2022: 19 · 2021: 19 · 2020: 27 · 2019: 19 · 2018: 26 · 2017: 12 · 2016: 10 · 2015: 20 · 2014: 10
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- National Institute of Biomedical Innovation
- Japan Society for the Promotion of Science (24659430)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- amyloid-beta oligomers, Alzheimer's disease, interleukin-1β processing, microglia, microglial neurotoxicity, reactive oxygen species, caspase-1, NLRP3 inflammasome, NADPH oxidase, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Central Nervous System, Amyloid beta-Peptides, Reactive Oxygen Species, Microglia, Mice, Interleukin-1beta
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