Abstract
Background: Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients. Results: mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1 β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production. Conclusions: The activation of at least two different inflammasome complexes explains AD-associated neuroinflammation. Strategies targeting inflammasome activation could be useful in the therapy of AD.
| Original language | English |
|---|---|
| Article number | 23 |
| Journal | Molecular Neurodegeneration |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- Alzheimer's disease
- Beta amyloid
- Inflammasome
- Mild cognitive impairment
- Neuroinflammation
ASJC Scopus subject areas
- Molecular Biology
- Clinical Neurology
- Cellular and Molecular Neuroscience
Cite this
The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease. / Saresella, Marina; La Rosa, Francesca; Piancone, Federica; Zoppis, Martina; Marventano, Ivana; Calabrese, Elena; Rainone, Veronica; Nemni, Raffaello; Mancuso, Roberta; Clerici, Mario Salvatore.
In: Molecular Neurodegeneration, Vol. 11, No. 1, 23, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease
AU - Saresella, Marina
AU - La Rosa, Francesca
AU - Piancone, Federica
AU - Zoppis, Martina
AU - Marventano, Ivana
AU - Calabrese, Elena
AU - Rainone, Veronica
AU - Nemni, Raffaello
AU - Mancuso, Roberta
AU - Clerici, Mario Salvatore
PY - 2016
Y1 - 2016
N2 - Background: Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients. Results: mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1 β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production. Conclusions: The activation of at least two different inflammasome complexes explains AD-associated neuroinflammation. Strategies targeting inflammasome activation could be useful in the therapy of AD.
AB - Background: Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients. Results: mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1 β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production. Conclusions: The activation of at least two different inflammasome complexes explains AD-associated neuroinflammation. Strategies targeting inflammasome activation could be useful in the therapy of AD.
KW - Alzheimer's disease
KW - Beta amyloid
KW - Inflammasome
KW - Mild cognitive impairment
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85007417755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007417755&partnerID=8YFLogxK
U2 - 10.1186/s13024-016-0088-1
DO - 10.1186/s13024-016-0088-1
M3 - Article
AN - SCOPUS:85007417755
VL - 11
JO - Molecular Neurodegeneration
JF - Molecular Neurodegeneration
SN - 1750-1326
IS - 1
M1 - 23
ER -