Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation
Abstract Alzheimer’s disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-β peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous spe...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Cell & Bioscience |
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| Online Access: | http://link.springer.com/article/10.1186/s13578-020-00474-4 |
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| author | Hariharakrishnan Chidambaram Rashmi Das Subashchandrabose Chinnathambi |
| author_facet | Hariharakrishnan Chidambaram Rashmi Das Subashchandrabose Chinnathambi |
| author_sort | Hariharakrishnan Chidambaram |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-β peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous species. Tau is a microtubule-binding protein that stabilizes tubulin to form microtubules under physiological condition. In AD/ pathological condition, Tau detaches from microtubules and aggregates to form oligomers of different sizes and filamentous species such as paired helical filaments. Microglia are the resident brain macrophages that are involved in the phagocytosis of microbes, cellular debris, misfolded and aggregated proteins. Chemokine receptor, CX3CR1 is mostly expressed on microglia and is involved in maintaining the microglia in a quiescent state by binding to its ligand, fractalkine (CX3CL1), which is expressed in neurons as both soluble or membrane-bound state. Hence, under physiological conditions, the CX3CR1/CX3CL1 axis plays a significant role in maintaining the central nervous system (CNS) homeostasis. Further, CX3CR1/CX3CL1 signalling is involved in the synthesis of anti-inflammatory cytokines and also has a significant role in cytoskeletal rearrangement, migration, apoptosis and proliferation. In AD brain, the expression level of fractalkine is reduced, and hence Tau competes to interact with its receptor, CX3CR1. In microglia, phagocytosis and internalization of extracellular Tau species occurs in the presence of a chemokine receptor, CX3CR1 which binds directly to Tau and promotes its internalization. In this review, the pathophysiological roles of CX3CR1/fractalkine signalling in microglia and neurons at different stages of Alzheimer’s disease and the possible role of CX3CR1/Tau signalling has been widely discussed. |
| first_indexed | 2024-12-11T00:23:34Z |
| format | Article |
| id | doaj.art-b1a55866d16d4f67aeafc711e06f411c |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-11T00:23:34Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-b1a55866d16d4f67aeafc711e06f411c2022-12-22T01:27:38ZengBMCCell & Bioscience2045-37012020-09-011011910.1186/s13578-020-00474-4Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferationHariharakrishnan Chidambaram0Rashmi Das1Subashchandrabose Chinnathambi2Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical LaboratoryNeurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical LaboratoryNeurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical LaboratoryAbstract Alzheimer’s disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-β peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous species. Tau is a microtubule-binding protein that stabilizes tubulin to form microtubules under physiological condition. In AD/ pathological condition, Tau detaches from microtubules and aggregates to form oligomers of different sizes and filamentous species such as paired helical filaments. Microglia are the resident brain macrophages that are involved in the phagocytosis of microbes, cellular debris, misfolded and aggregated proteins. Chemokine receptor, CX3CR1 is mostly expressed on microglia and is involved in maintaining the microglia in a quiescent state by binding to its ligand, fractalkine (CX3CL1), which is expressed in neurons as both soluble or membrane-bound state. Hence, under physiological conditions, the CX3CR1/CX3CL1 axis plays a significant role in maintaining the central nervous system (CNS) homeostasis. Further, CX3CR1/CX3CL1 signalling is involved in the synthesis of anti-inflammatory cytokines and also has a significant role in cytoskeletal rearrangement, migration, apoptosis and proliferation. In AD brain, the expression level of fractalkine is reduced, and hence Tau competes to interact with its receptor, CX3CR1. In microglia, phagocytosis and internalization of extracellular Tau species occurs in the presence of a chemokine receptor, CX3CR1 which binds directly to Tau and promotes its internalization. In this review, the pathophysiological roles of CX3CR1/fractalkine signalling in microglia and neurons at different stages of Alzheimer’s disease and the possible role of CX3CR1/Tau signalling has been widely discussed.http://link.springer.com/article/10.1186/s13578-020-00474-4Alzheimer’s diseaseMicrogliaNeuronTauFractalkineCX3CR1 receptor |
| spellingShingle | Hariharakrishnan Chidambaram Rashmi Das Subashchandrabose Chinnathambi Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation Cell & Bioscience Alzheimer’s disease Microglia Neuron Tau Fractalkine CX3CR1 receptor |
| title | Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation |
| title_full | Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation |
| title_fullStr | Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation |
| title_full_unstemmed | Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation |
| title_short | Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation |
| title_sort | interaction of tau with the chemokine receptor cx3cr1 and its effect on microglial activation migration and proliferation |
| topic | Alzheimer’s disease Microglia Neuron Tau Fractalkine CX3CR1 receptor |
| url | http://link.springer.com/article/10.1186/s13578-020-00474-4 |
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