Role of galectin-3 in prion infections of the CNS

Mok, Simon Wing-Fai; Riemer, Constanze; Madela, Kazimierz; Hsu, Daniel K.; Liu, Fu‐Tong; Gültner, Sandra; Heise, Ines; Baier, Michael

doi:10.1016/j.bbrc.2007.05.163

Cited by 58 publications

(49 citation statements)

References 34 publications

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“…Long-term treatment of cells with 100 mM trehalose (14 days) showed that reduction of PrP Sc is not a transient phenomenon ( prion-infected brain tissue a slight reduction in expression of genes mediating autophagy. 44 In recent studies, we have shown that treatment of prion-infected cells with imatinib activates lysosomal degradation of PrP Sc . 45 In another study, we demonstrated that imatinib can induce the formation of autophagosomes.…”

Section: Resultsmentioning

confidence: 99%

“…41 However, data on autophagy in prion diseases are still very limited. [13][14][15][16][17][42][43][44] Electron microscopy studies pointed towards a possible contribution of autophagy in prion disease-associated neurodegeneration, whereas others observed in Autophagy and cellular prion infection www.landesbioscience.com Autophagy(30 and 60 days), this effect was not evident at later time points (e.g., 90 days p.i. ), and prion incubation times of trehalose-and sucrose-treated animals were not different from that of mock-treated mice.…”

Section: Discussionmentioning

confidence: 99%

“…Intraperitoneal infections of mice were performed as previously described. 44 Trehalose or the control disaccharide sucrose was thereafter continuously administered as 4% solutions via the drinking water (ad libitum). Spleens of individual mice were analyzed in immunoblot at different time points for PrP Sc and incubation times to clinical prion infection monitored as described.…”

Section: Methodsmentioning

confidence: 99%

“…Spleens of individual mice were analyzed in immunoblot at different time points for PrP Sc and incubation times to clinical prion infection monitored as described. 44 Trypan blue assay. To assess viability of cells upon 100 mM trehalose treatment, trypan blue assay was performed.…”

Section: Methodsmentioning

confidence: 99%

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Autophagy induction by trehalose counter-acts cellular prion-infection

Aguib

Heiseke²,

Gilch³

et al. 2009

Autophagy

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy induction by trehalose counter-acts cellular prion-infection

Aguib

Heiseke²,

Gilch³

et al. 2009

Autophagy

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204

159

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“…Among them are galectins, a family of secreted proteins that recognize and bind to galactose and its derivatives (53). A similar mechanism could also play a role in clearing PrP Sc with deficient sialylation status (54,55). Alternative mechanisms might involve inhibitory Siglecs that recognize sialic acid patterns and suppress innate immune cells (56,57), and/or factor H that dampens activation of alternative complement pathways by recognizing molecular patterns containing sialic acids on surfaces of host cells or pathogens (58, 59).…”

Section: Figure 4 Analysis Of Prpmentioning

confidence: 99%

Sialylation Controls Prion Fate in Vivo

Srivastava

Katorcha

Daus

et al. 2017

Journal of Biological Chemistry

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Edited by Paul E. Fraser Prions or PrPSc are proteinaceous infectious agents that consist of misfolded, self-replicating states of a sialoglycoprotein called the prion protein or PrP C . The current work tests a new hypothesis that sialylation determines the fate of prions in an organism. To begin, we produced control PrP Sc from PrP C using protein misfolding cyclic amplification with beads (PMCAb), and also generated PrP Sc with reduced sialylation levels using the same method but with partially desialylated PrP C as a substrate (dsPMCAb (22,23). Sialylated glycans play an essential role in a broad range of cellular functions, but are especially important in immunity (24). Terminal sialic acid residues on the surface of mammalian cells act as a part of a "self-associated molecular pattern," providing molecular cues to the immune system for discriminating between "self," "altered self," or "non-self" (25, 26). Glycoproteins or glycolipids that lack sialic acids at terminal positions serve as a "pathogen-associated molecular pattern" used by mammalian immune systems to recognize pathogens or asialoglycoproteins that need to be removed (25). Bearing in mind that sialylation serves as a molecular marker of self versus nonself, we proposed a hypothesis that sialylation determines the fate of prions in an organism (27)

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Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1^G93A mouse model of amyotrophic lateral sclerosis

et al. 2012

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Galectins are pleiotropic carbohydrate-binding lectins involved in inflammation, growth/differentiation, and tissue remodeling. The functional role of galectins in amyotrophic lateral sclerosis (ALS) is unknown. Expression studies revealed increases in galectin-1 mRNA and protein in spinal cords from SOD1G93A mice, and in galectin-3 and -9 mRNAs and proteins in spinal cords of both SOD1G93A mice and sporadic ALS patients. As the increase in galectin-3 appeared in early presymptomatic stages and increased progressively through to end stage of disease in the mouse, it was selected for additional study, where it was found to be mainly expressed by microglia. Galectin-3 antagonists are not selective and do not readily cross the blood–brain barrier; therefore, we generated SOD1G93A/Gal-3−/− transgenic mice to evaluate galectin-3 deletion in a widely used mouse model of ALS. Disease progression, neurological symptoms, survival, and inflammation were assessed to determine the effect of galectin-3 deletion on the SOD1G93A disease phenotype. Galectin-3 deletion did not change disease onset, but resulted in more rapid progression through functionally defined disease stages, more severely impaired neurological symptoms at all stages of disease, and expiration, on average, 25 days earlier than SOD1G93A/Gal-3+/+ cohorts. In addition, microglial staining, as well as TNF-α, and oxidative injury were increased in SOD1G93A/Gal-3−/− mice compared with SOD1G93A/Gal-3+/+ cohorts. These data support an important functional role for microglial galectin-3 in neuroinflammation during chronic neurodegenerative disease. We suggest that elevations in galectin-3 by microglia as disease progresses may represent a protective, anti-inflammatory innate immune response to chronic motor neuron degeneration.

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Role of galectin-3 in prion infections of the CNS

Cited by 58 publications

References 34 publications

Autophagy induction by trehalose counter-acts cellular prion-infection

Autophagy induction by trehalose counter-acts cellular prion-infection

Sialylation Controls Prion Fate in Vivo

Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1^G93A mouse model of amyotrophic lateral sclerosis

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Role of galectin-3 in prion infections of the CNS

Cited by 58 publications

References 34 publications

Autophagy induction by trehalose counter-acts cellular prion-infection

Autophagy induction by trehalose counter-acts cellular prion-infection

Sialylation Controls Prion Fate in Vivo

Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1G93A mouse model of amyotrophic lateral sclerosis

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Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1^G93A mouse model of amyotrophic lateral sclerosis