The association between prion proteins and Aβ1–42 oligomers in cytotoxicity and apoptosis

Hyeon, Jae Wook; Kim, Su Yeon; Park, Jun-Sun; Choi, Bo Yeong; Lee, Sol Moe; Ju, Young Ran; An, Seong Soo A.; Kim, Chi-Kyeong

doi:10.1016/j.bbrc.2012.06.056

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…In addition, a multitude of research has demonstrated that Aβ binding to PrP c leads to the induction of apoptosis through an upregulation of pro-apoptotic proteins such as Bax40, enhanced Ca 2+ release into the cytosol41 and the activation of caspases- particularly caspase 841. However, these pro-apoptotic signals may not be directly transduced by PrP c as it is not a transmembrane protein and therefore must be transduced through receptors to which PrP c binds.…”

Section: Discussionmentioning

confidence: 99%

The 37kDa/67kDa Laminin Receptor acts as a receptor for Aβ42 internalization

Dias

Jovanović

Gonsalves

et al. 2014

Sci Rep

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Neuronal loss is a major neuropathological hallmark of Alzheimer's disease (AD). The associations between soluble Aβ oligomers and cellular components cause this neurotoxicity. The 37 kDa/67 kDa laminin receptor (LRP/LR) has recently been implicated in Aβ pathogenesis. In this study the mechanism underlying the pathological role of LRP/LR was elucidated. Försters Resonance Energy Transfer (FRET) revealed that LRP/LR and Aβ form a biologically relevant interaction. The ability of LRP/LR to form stable associations with endogenously shed Aβ was confirmed by pull down assays and Aβ-ELISAs. Antibody blockade of this association significantly lowered Aβ42 induced apoptosis. Furthermore, antibody blockade and shRNA mediated downregulation of LRP/LR significantly hampered Aβ42 internalization. These results suggest that LRP/LR is a receptor for Aβ42 internalization, mediating its endocytosis and contributing to the cytotoxicity of the neuropeptide by facilitating intra-cellular Aβ42 accumulation. These findings recommend anti-LRP/LR specific antibodies and shRNAs as potential therapeutic tools for AD treatment.

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Section: Discussionmentioning

confidence: 99%

The 37kDa/67kDa Laminin Receptor acts as a receptor for Aβ42 internalization

Dias

Jovanović

Gonsalves

et al. 2014

Sci Rep

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“…42,43 In agreement with Hyeon (2012) it is postulated that moPrP might play a role in induction of apoptosis and in the activation of antibacterial responses in the presence of LPS or other DAMPs in the microenvironment. 44 Overall, the results from this study showed that applying moPrP to the mucosal side of the colon of male FVB/N mice using an Ussing chamber system induces expression of genes related to the JNK and p38 signaling cascade. In addition, moPrP strongly upregulated expression of the antimicrobial peptide Slpi, which suggests that the prion protein might serve as a 'danger signal' for the presence of bacteria.…”

mentioning

confidence: 83%

Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice

Dervishi

Lam

Dunn

et al. 2015

Prion

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ABSTRACT. The objectives of this study were to test whether recombinant mouse (mo)PrP alone or in combination with LPS or under simulated endotoxemia would affect expression of genes related to host inflammatory and antimicrobial responses. To test our hypotheses colon tissues were collected from 16 male mice (FVB/N strain) and mounted in an Ussing chamber. Application of moPrP to the mucosal side of the colon affected genes related to TLR-and NLR-signaling and antimicrobial responses. When LPS was added on the mucosal side of the colon, genes related to TLR, Nlrp3 inflammasome, and iron transport proteins were over-expressed. Addition of LPS to the serosal side of the colon up-regulated genes related to TLR-and NLR-signaling, Nlrp3 inflammasome, and a chemokine. Treatment with both moPrP and LPS to the mucosal side of the colon upregulated genes associated with TLR, downstream signal transduction (DST), inflammatory response, attraction of dendritic cells to the site of inflammation, and the JNK-apoptosis pathway. Administration of moPrP to the mucosal side and LPS to the serosal side of the colon affected genes related to TLR-and NLRsignaling, DST, apoptosis, inflammatory response, cytokines, chemokines, and antimicrobial peptides. Overall this study suggests a potential role for moPrP as an endogenous 'danger signal' associated with activation of colon genes related to innate immunity and antibacterial responses.

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“…Lastly, there are antioxidant assays that will quantify the levels of ascorbic acid, tocopherols, GSH, GSSG, uric acid, and total antioxidant capacity (TAC) (Zhang et al, 2012). All of the stated biomolecules above are biomarkers for various metal oxide nanoparticle species (Hyeon et al, 2012).…”

Section: Methods To Test For Biomarkers Of Nanotoxicitymentioning

confidence: 99%