New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention
Alzheimer’s disease (AD) is the most common form of dementia, affecting more than 50 million people worldwide with an estimated increase to 139 million people by 2050. The exact pathogenic mechanisms of AD remain elusive, resulting in the fact that the current therapeutics solely focus on symptomati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/12/1925 |
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| author | Tiantian Li Li Lu Eloise Pember Xinuo Li Bocheng Zhang Zheying Zhu |
| author_facet | Tiantian Li Li Lu Eloise Pember Xinuo Li Bocheng Zhang Zheying Zhu |
| author_sort | Tiantian Li |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common form of dementia, affecting more than 50 million people worldwide with an estimated increase to 139 million people by 2050. The exact pathogenic mechanisms of AD remain elusive, resulting in the fact that the current therapeutics solely focus on symptomatic management instead of preventative or curative strategies. The two most widely accepted pathogenic mechanisms of AD include the amyloid and tau hypotheses. However, it is evident that these hypotheses cannot fully explain neuronal degeneration shown in AD. Substantial evidence is growing for the vital role of neuroinflammation in AD pathology. The neuroinflammatory hypothesis provides a new, exciting lead in uncovering the underlying mechanisms contributing to AD. This review aims to highlight new insights into the role of neuroinflammation in the pathogenesis of AD, mainly including the involvement of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3)/caspase-1 axis, triggering receptor expressed on myeloid cells 2 (TREM2) and cGAS-STING as key influencers in augmenting AD development. The inflammasomes related to the pathways of NF-κB, NLRP3, TREM2, and cGAS-STING as biomarkers of the neuroinflammation associated with AD, as well as an overview of novel AD treatments based on these biomarkers as potential drug targets reported in the literature or under clinical trials, are explored. |
| first_indexed | 2024-03-10T00:10:15Z |
| format | Article |
| id | doaj.art-92bd4d15486f4ce08f00662dfc254bd9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:10:15Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-92bd4d15486f4ce08f00662dfc254bd92023-11-23T16:01:38ZengMDPI AGCells2073-44092022-06-011112192510.3390/cells11121925New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic InterventionTiantian Li0Li Lu1Eloise Pember2Xinuo Li3Bocheng Zhang4Zheying Zhu5School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, China Pharmaceutical University, Nanjing 211112, ChinaSchool of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UKAlzheimer’s disease (AD) is the most common form of dementia, affecting more than 50 million people worldwide with an estimated increase to 139 million people by 2050. The exact pathogenic mechanisms of AD remain elusive, resulting in the fact that the current therapeutics solely focus on symptomatic management instead of preventative or curative strategies. The two most widely accepted pathogenic mechanisms of AD include the amyloid and tau hypotheses. However, it is evident that these hypotheses cannot fully explain neuronal degeneration shown in AD. Substantial evidence is growing for the vital role of neuroinflammation in AD pathology. The neuroinflammatory hypothesis provides a new, exciting lead in uncovering the underlying mechanisms contributing to AD. This review aims to highlight new insights into the role of neuroinflammation in the pathogenesis of AD, mainly including the involvement of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3)/caspase-1 axis, triggering receptor expressed on myeloid cells 2 (TREM2) and cGAS-STING as key influencers in augmenting AD development. The inflammasomes related to the pathways of NF-κB, NLRP3, TREM2, and cGAS-STING as biomarkers of the neuroinflammation associated with AD, as well as an overview of novel AD treatments based on these biomarkers as potential drug targets reported in the literature or under clinical trials, are explored.https://www.mdpi.com/2073-4409/11/12/1925Alzheimer’s diseaseneuroinflammationNF-κBNLRP3TREM2cGAS-STING |
| spellingShingle | Tiantian Li Li Lu Eloise Pember Xinuo Li Bocheng Zhang Zheying Zhu New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention Cells Alzheimer’s disease neuroinflammation NF-κB NLRP3 TREM2 cGAS-STING |
| title | New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention |
| title_full | New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention |
| title_fullStr | New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention |
| title_full_unstemmed | New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention |
| title_short | New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer’s Disease and Its Potential for Therapeutic Intervention |
| title_sort | new insights into neuroinflammation involved in pathogenic mechanism of alzheimer s disease and its potential for therapeutic intervention |
| topic | Alzheimer’s disease neuroinflammation NF-κB NLRP3 TREM2 cGAS-STING |
| url | https://www.mdpi.com/2073-4409/11/12/1925 |
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