Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment
Alzheimer’s disease (AD) is the most common cause of dementia in the general population and, to date, constitutes a major therapeutic challenge. In the pathogenesis of AD, aggregates of amyloid β (Aβ) and neurofibrillary tangles (NFTs) containing Tau-microtubule-associated protein (tau) are known to...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8979 |
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| author | Julia Barczuk Natalia Siwecka Weronika Lusa Wioletta Rozpędek-Kamińska Ewa Kucharska Ireneusz Majsterek |
| author_facet | Julia Barczuk Natalia Siwecka Weronika Lusa Wioletta Rozpędek-Kamińska Ewa Kucharska Ireneusz Majsterek |
| author_sort | Julia Barczuk |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common cause of dementia in the general population and, to date, constitutes a major therapeutic challenge. In the pathogenesis of AD, aggregates of amyloid β (Aβ) and neurofibrillary tangles (NFTs) containing Tau-microtubule-associated protein (tau) are known to trigger a neuroinflammatory response with subsequent formation of an inflammasome. In particular, the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is thought to play a crucial role in AD-related pathology. While the mechanisms for NLRP3 activation are not fully understood, it has been demonstrated that, after detection of protein aggregates, NLRP3 induces pro-inflammatory cytokines, such as interleukin 18 (IL-18) or interleukin 1β (IL-1β), that further potentiate AD progression. Specific inhibitors of NLRP3 that exhibit various mechanisms to attenuate the activity of NLRP3 have been tested in in vivo studies and have yielded promising results, as shown by the reduced level of tau and Aβ aggregates and diminished cognitive impairment. Herein, we would like to summarize the current state of knowledge on NLRP3 inflammasome priming, activation, and its actual role in AD pathogenesis, and to characterize the NLRP3 inhibitors that have been studied most and their impact on AD-related pathology. |
| first_indexed | 2024-03-09T13:18:57Z |
| format | Article |
| id | doaj.art-ed8a9fb9a22240ccae5cbb506464b3de |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:18:57Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ed8a9fb9a22240ccae5cbb506464b3de2023-11-30T21:33:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316897910.3390/ijms23168979Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease TreatmentJulia Barczuk0Natalia Siwecka1Weronika Lusa2Wioletta Rozpędek-Kamińska3Ewa Kucharska4Ireneusz Majsterek5Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, PolandDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, PolandDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, PolandDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, PolandDepartment of Gerontology, Geriatrics and Social Work, Jesuit University Ignatianum, 31-501 Krakow, PolandDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, PolandAlzheimer’s disease (AD) is the most common cause of dementia in the general population and, to date, constitutes a major therapeutic challenge. In the pathogenesis of AD, aggregates of amyloid β (Aβ) and neurofibrillary tangles (NFTs) containing Tau-microtubule-associated protein (tau) are known to trigger a neuroinflammatory response with subsequent formation of an inflammasome. In particular, the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is thought to play a crucial role in AD-related pathology. While the mechanisms for NLRP3 activation are not fully understood, it has been demonstrated that, after detection of protein aggregates, NLRP3 induces pro-inflammatory cytokines, such as interleukin 18 (IL-18) or interleukin 1β (IL-1β), that further potentiate AD progression. Specific inhibitors of NLRP3 that exhibit various mechanisms to attenuate the activity of NLRP3 have been tested in in vivo studies and have yielded promising results, as shown by the reduced level of tau and Aβ aggregates and diminished cognitive impairment. Herein, we would like to summarize the current state of knowledge on NLRP3 inflammasome priming, activation, and its actual role in AD pathogenesis, and to characterize the NLRP3 inhibitors that have been studied most and their impact on AD-related pathology.https://www.mdpi.com/1422-0067/23/16/8979Alzheimer’s diseaseamyloid βneurofibrillary tanglesNOD-like receptor pyrin domain-containing 3NOD-like receptor pyrin domain-containing 3 inflammasomeNOD-like receptor pyrin domain-containing 3 inhibitors |
| spellingShingle | Julia Barczuk Natalia Siwecka Weronika Lusa Wioletta Rozpędek-Kamińska Ewa Kucharska Ireneusz Majsterek Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment International Journal of Molecular Sciences Alzheimer’s disease amyloid β neurofibrillary tangles NOD-like receptor pyrin domain-containing 3 NOD-like receptor pyrin domain-containing 3 inflammasome NOD-like receptor pyrin domain-containing 3 inhibitors |
| title | Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment |
| title_full | Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment |
| title_fullStr | Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment |
| title_full_unstemmed | Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment |
| title_short | Targeting NLRP3-Mediated Neuroinflammation in Alzheimer’s Disease Treatment |
| title_sort | targeting nlrp3 mediated neuroinflammation in alzheimer s disease treatment |
| topic | Alzheimer’s disease amyloid β neurofibrillary tangles NOD-like receptor pyrin domain-containing 3 NOD-like receptor pyrin domain-containing 3 inflammasome NOD-like receptor pyrin domain-containing 3 inhibitors |
| url | https://www.mdpi.com/1422-0067/23/16/8979 |
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