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Galectin-3, a novel...
Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
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- Boza-Serrano, Antonio (author)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Ruiz, Rocío (author)
- University of Seville
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- Sanchez-Varo, Raquel (author)
- University of Malaga
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- García-Revilla, Juan (author)
- University of Seville
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- Yang, Yiyi (author)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Jimenez-Ferrer, Itzia (author)
- Lund University,Lunds universitet,Translationell Neurogenetik,Forskargrupper vid Lunds universitet,Translational Neurogenetics,Lund University Research Groups
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- Paulus, Agnes (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Neuroinflammation,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Lund University Research Groups
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- Wennström, Malin (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Vilalta, Anna (author)
- University of Cambridge
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- Allendorf, David (author)
- University of Cambridge
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- Davila, Jose Carlos (author)
- University of Malaga
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- Stegmayr, John (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,Lung Bioengineering and Regeneration,Lund University Research Groups
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- Jiménez, Sebastian (author)
- University of Seville,CIBER Enfermedades Neurodegenerativas (CIBERNED)
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- Roca-Ceballos, Maria A. (author)
- University of Seville
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- Navarro-Garrido, Victoria (author)
- University of Seville,CIBER Enfermedades Neurodegenerativas (CIBERNED)
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- Swanberg, Maria (author)
- Lund University,Lunds universitet,Translationell Neurogenetik,Forskargrupper vid Lunds universitet,Translational Neurogenetics,Lund University Research Groups
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- Hsieh, Christine L. (author)
- University of California, San Francisco
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- Real, Luis M. (author)
- Valme University Hospital
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- Englund, Elisabet (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Linse, Sara (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Leffler, Hakon (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Nilsson, Ulf J. (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Brown, Guy C. (author)
- University of Cambridge
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- Gutierrez, Antonia (author)
- University of Malaga
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- Vitorica, Javier (author)
- CIBER Enfermedades Neurodegenerativas (CIBERNED),University of Seville
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- Venero, Jose Luis (author)
- University of Seville
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- Deierborg, Tomas (author)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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(creator_code:org_t)
- 2019-04-20
- 2019
- English.
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
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Abstract
Subject headings
Close
- Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer’s disease (AD)
- Amyloid aggregation
- Galectin-3
- Inflammation
- Microglia
- TREM2
Publication and Content Type
- art (subject category)
- ref (subject category)
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Boza-Serrano, An ...
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Ruiz, Rocío
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Sanchez-Varo, Ra ...
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García-Revilla, ...
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Yang, Yiyi
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Jimenez-Ferrer, ...
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show more...
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Paulus, Agnes
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Wennström, Malin
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Vilalta, Anna
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Allendorf, David
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Davila, Jose Car ...
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Stegmayr, John
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Jiménez, Sebasti ...
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Roca-Ceballos, M ...
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Navarro-Garrido, ...
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Swanberg, Maria
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Hsieh, Christine ...
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Real, Luis M.
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Englund, Elisabe ...
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Linse, Sara
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Leffler, Hakon
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Nilsson, Ulf J.
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Brown, Guy C.
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Gutierrez, Anton ...
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Vitorica, Javier
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Venero, Jose Lui ...
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Deierborg, Tomas
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Neurosciences
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Acta Neuropathol ...
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