Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease

Wang, Xuexin; Zhang, Shuping; Lin, Faliang; Chu, Wenzheng; Yue, Shouwei

doi:10.1177/1533317513495107

Cited by 80 publications

(69 citation statements)

References 35 publications

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“…These results are consistent with reports that integrin and integrin-associated protein facilitate LTP and memory performance in rats (Staubli et al, 1990; Huang et al, 1998). They are also congruent with the finding that galectin-3 levels are increased in the serum of Alzheimer’s disease patients (Wang et al, 2015). Further support comes from the observations that a lack of galectin-3 facilitates motor function recovery after spinal cord injury (Mostacada et al, 2015), and that galectin-3 contributes to hypoxic-ischemia injury and ischemia-induced neuronal death (Doverhag et al, 2010; Satoh et al, 2011), findings that suggest a role for galectin-3 in negative regulation of neuronal plasticity.…”

Section: Discussionsupporting

confidence: 89%

Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation

Chen

Lin

et al. 2017

Front. Mol. Neurosci.

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Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms.

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Section: Discussionsupporting

confidence: 89%

Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation

Chen

Lin

et al. 2017

Front. Mol. Neurosci.

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“…Similarly we recently reported that LPS increases the expression of galectins within the mouse brain (Brooks et al, 2016a). The galectins are a group of lectins that have been implicated in several central diseases and neurological disorders (John and Mishra, 2016; Liu and Rabinovich, 2010; Lutomski et al, 1997; Stancic et al, 2011; Wang et al, 2015b). Like, corticosteroids, Gal-9 interacted with IFNγ to accentuate Ido1-FL expression (Brooks et al, 2016a).…”

Section: Discussionmentioning

confidence: 99%

Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases

Brooks

Janda

Lawson

et al. 2017

Brain, Behavior, and Immunity

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Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential. The Kynurenine Pathway produces tryptophan metabolites that modulate neurotransmitter activity. This recognition identified another putative pathway for anti-depressant targeting. Considering a recognized role of the Kynurenine Pathway in depression, we investigated the potential for Desip to alter expression of rate-limiting enzymes of this pathway: indoleamine-2,3-dioxygenases (Ido1 and Ido2). Mice were administered lipopolysaccharide (LPS) or synthetic glucocorticoid dexamethasone (Dex) with Desip to determine if Desip alters indoleamine-dioxygenase (DO) expression in vivo following a modeled immune and stress response. This work was followed by treating murine and human peripheral blood mononuclear cells (PBMCs) with interferon-gamma (IFNγ) and Desip. In vivo: Desip blocked LPS-induced Ido1 expression in hippocampi, astrocytes, microglia and PBMCs and Ido2 expression by PBMCs. Ex vivo: Desip decreased IFNγ-induced Ido1 and Ido2 expression in murine PBMCs. This effect was directly translatable to the human system as Desip decreased IDO1 and IDO2 expression by human PBMCs. These data demonstrate for the first time that an anti-depressant alters expression of Ido1 and Ido2, identifying a possible new mechanism behind anti-depressant activity. Furthermore, we propose the assessment of PBMCs for anti-depressant responsiveness using IDO expression as a biomarker.

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“…Increased levels of serum Gal-3 is not limited to cancer as it has been associated with other diseases such as systemic lupus erythematosus, rheumatoid arthritis, Alzheimer's disease and Behçet's disease (15-17). Circulating Gal-3 was positively associated with the type 2 diabetes, which could be reduced by anti-diabetes metformin (19).…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 induces cell migration via a calcium-sensitive MAPK/ERK1/2 pathway

et al. 2014

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The presence and level of circulating galectin-3 (Gal-3), a member of the galectin family, is associated with diverse diseases ranging from heart failure, immune disorders to cancer metastasis and serves as a biomarker of diagnosis and treatment response. However, the mechanisms by which exogenous Gal-3 affects pathobiology events remain elusive. In the current study, we found that exogenous Gal-3 slightly delays, while prolonging tyrosine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cells through a calcium-sensitive and PKC-dependent signaling pathway. The activation was dependent on the sugar-binding properties of Gal-3, since the antagonist lactose could inhibit it. The sugar-binding motif of Gal-3 was required for the activation of ERK1/2. The activation of ERK1/2 was necessary for the initiation and induction of cell migration associated with the phosphorylation of paxillin. All the results presented in this study suggest a novel calcium-sensitive and PKC-dependent pathway through which circulating Gal-3 promotes cell migration and activating the ERK1/2. Taken together, the data depicted here propose a biological function and a target for the diseases' associated circulating Gal-3.

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Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease

Cited by 80 publications

References 35 publications

Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation

Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation

Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases

Galectin-3 induces cell migration via a calcium-sensitive MAPK/ERK1/2 pathway

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