Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease
The inflammatory response that marks Alzheimer’s disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory pr...
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MDPI AG
2023-07-01
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author | Bartolo Tamburini Giusto Davide Badami Marco Pio La Manna Mojtaba Shekarkar Azgomi Nadia Caccamo Francesco Dieli |
author_facet | Bartolo Tamburini Giusto Davide Badami Marco Pio La Manna Mojtaba Shekarkar Azgomi Nadia Caccamo Francesco Dieli |
author_sort | Bartolo Tamburini |
collection | DOAJ |
description | The inflammatory response that marks Alzheimer’s disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory process which impairs β-amyloid peptide clearance capability and leads to neurotoxicity and neurodegeneration. Moreover, microglia also appear to be closely involved in the spread of tau pathology. Soluble TREM2 also represents a crucial player in the neuroinflammatory processes. Elevated levels of TREM2 in cerebrospinal fluid have been associated with increased amyloid plaque burden, neurodegeneration, and cognitive decline in individuals with Alzheimer’s disease. Understanding the intricate relationship between innate immunity and Alzheimer’s disease will be a promising strategy for future advancements in diagnosis and new therapeutic interventions targeting innate immunity, by modulating its activity. Still, additional and more robust studies are needed to translate these findings into effective treatments. In this review, we focus on the role of cells (microglia, astrocytes, and oligodendrocytes) and molecules (TREM2, tau, and β-amyloid) of the innate immune system in the pathogenesis of Alzheimer’s disease and their possible exploitation as disease biomarkers and targets of therapeutical approaches. |
first_indexed | 2024-03-11T00:26:47Z |
format | Article |
id | doaj.art-c89edaa3223648a39b382a6a1de09d0b |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T00:26:47Z |
publishDate | 2023-07-01 |
publisher | MDPI AG |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-c89edaa3223648a39b382a6a1de09d0b2023-11-18T22:57:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151192210.3390/ijms241511922Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s DiseaseBartolo Tamburini0Giusto Davide Badami1Marco Pio La Manna2Mojtaba Shekarkar Azgomi3Nadia Caccamo4Francesco Dieli5Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, ItalyThe inflammatory response that marks Alzheimer’s disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory process which impairs β-amyloid peptide clearance capability and leads to neurotoxicity and neurodegeneration. Moreover, microglia also appear to be closely involved in the spread of tau pathology. Soluble TREM2 also represents a crucial player in the neuroinflammatory processes. Elevated levels of TREM2 in cerebrospinal fluid have been associated with increased amyloid plaque burden, neurodegeneration, and cognitive decline in individuals with Alzheimer’s disease. Understanding the intricate relationship between innate immunity and Alzheimer’s disease will be a promising strategy for future advancements in diagnosis and new therapeutic interventions targeting innate immunity, by modulating its activity. Still, additional and more robust studies are needed to translate these findings into effective treatments. In this review, we focus on the role of cells (microglia, astrocytes, and oligodendrocytes) and molecules (TREM2, tau, and β-amyloid) of the innate immune system in the pathogenesis of Alzheimer’s disease and their possible exploitation as disease biomarkers and targets of therapeutical approaches.https://www.mdpi.com/1422-0067/24/15/11922microgliaAlzheimer’s diseaseneuroinflammation |
spellingShingle | Bartolo Tamburini Giusto Davide Badami Marco Pio La Manna Mojtaba Shekarkar Azgomi Nadia Caccamo Francesco Dieli Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease International Journal of Molecular Sciences microglia Alzheimer’s disease neuroinflammation |
title | Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease |
title_full | Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease |
title_fullStr | Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease |
title_full_unstemmed | Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease |
title_short | Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease |
title_sort | emerging roles of cells and molecules of innate immunity in alzheimer s disease |
topic | microglia Alzheimer’s disease neuroinflammation |
url | https://www.mdpi.com/1422-0067/24/15/11922 |
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