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Role of cGAS–Sting Signaling in Alzheimer’s Disease

There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and...

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Autores principales: Govindarajulu, Manoj, Ramesh, Sindhu, Beasley, McNeil, Lynn, Graham, Wallace, Caleigh, Labeau, Sammie, Pathak, Suhrud, Nadar, Rishi, Moore, Timothy, Dhanasekaran, Muralikrishnan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179704/
https://www.ncbi.nlm.nih.gov/pubmed/37175853
http://dx.doi.org/10.3390/ijms24098151
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author Govindarajulu, Manoj
Ramesh, Sindhu
Beasley, McNeil
Lynn, Graham
Wallace, Caleigh
Labeau, Sammie
Pathak, Suhrud
Nadar, Rishi
Moore, Timothy
Dhanasekaran, Muralikrishnan
author_facet Govindarajulu, Manoj
Ramesh, Sindhu
Beasley, McNeil
Lynn, Graham
Wallace, Caleigh
Labeau, Sammie
Pathak, Suhrud
Nadar, Rishi
Moore, Timothy
Dhanasekaran, Muralikrishnan
author_sort Govindarajulu, Manoj
collection PubMed
description There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS–STING signaling pathway and the mechanisms underlying the association between cGAS–STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS–STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS–STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs
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spelling pubmed-101797042023-05-13 Role of cGAS–Sting Signaling in Alzheimer’s Disease Govindarajulu, Manoj Ramesh, Sindhu Beasley, McNeil Lynn, Graham Wallace, Caleigh Labeau, Sammie Pathak, Suhrud Nadar, Rishi Moore, Timothy Dhanasekaran, Muralikrishnan Int J Mol Sci Review There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS–STING signaling pathway and the mechanisms underlying the association between cGAS–STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS–STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS–STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs MDPI 2023-05-02 /pmc/articles/PMC10179704/ /pubmed/37175853 http://dx.doi.org/10.3390/ijms24098151 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Govindarajulu, Manoj
Ramesh, Sindhu
Beasley, McNeil
Lynn, Graham
Wallace, Caleigh
Labeau, Sammie
Pathak, Suhrud
Nadar, Rishi
Moore, Timothy
Dhanasekaran, Muralikrishnan
Role of cGAS–Sting Signaling in Alzheimer’s Disease
title Role of cGAS–Sting Signaling in Alzheimer’s Disease
title_full Role of cGAS–Sting Signaling in Alzheimer’s Disease
title_fullStr Role of cGAS–Sting Signaling in Alzheimer’s Disease
title_full_unstemmed Role of cGAS–Sting Signaling in Alzheimer’s Disease
title_short Role of cGAS–Sting Signaling in Alzheimer’s Disease
title_sort role of cgas–sting signaling in alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179704/
https://www.ncbi.nlm.nih.gov/pubmed/37175853
http://dx.doi.org/10.3390/ijms24098151
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