Prion Interaction with the 37-kDa/67-kDa Laminin Receptor on Enterocytes as a Cellular Model for Intestinal Uptake of Prions

Kolodziejczak, Dominika; Dias, Bianca Da Costa; Zuber, Chantal; Jovanović, Katarina; Omar, Aadilah; Beck, Julia; Vana, Karen; Mbazima, Vusi; Richt, Jüergen A.; Brenig, Bertram; Weiß, Stefan

doi:10.1016/j.jmb.2010.06.055

Cited by 22 publications

(29 citation statements)

References 40 publications

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“…26,27 As the infectious prion isoform is reported to be present in the blood 28 and skeletal muscle, 29 hunting, consumption of wild venison and contact with other animal products derived from CWD-infected elk and deer may thereby pose a public health risk. Our studies demonstrate that PrP CWD co-localizes with LRP/LR on human enterocytes 24 thereby suggesting a possible oral transmissibilty of this TSE to humans. This is, however, inconsistent with results obtained during intra-cerebral inoculation of the brains and spinal cords of transgenic mice overexpressing the human cellular prion protein (PrP c ), 26,27 which is essential for TSE disease establishment and progression.…”

Section: Alimentary Prion Infectionsmentioning

confidence: 65%

“…25 These results, due to the evolutionary relatedness between macaques and humans, allowed researchers to confirm the oral transmissibility of PrP BSE to humans. PrP BSE may also potentially lead to prion disorder establishment in swine, 24 livestock of great economic and social importance.…”

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

“…24 Moreover, the blockage of such interactions through the use of anti-LRP/LR specific antibodies has been reported to reduce PrP Sc endocytosis 19 and thus these antibodies may serve as potential therapeutics to prevent infectious prion internalization and thereby prevent prion infections. It must be emphasized that the adhesion of prion proteins to cells is not solely dependent on the LRP/LR-PrP Sc interactions; 24 however, this interaction is of importance with regards to internalization and subsequent pathogenesis.…”

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

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Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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N eurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets that accumulate in the central nervous system. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs)-also termed prion disorders-afflict a substantial proportion of the human population and, as such, the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies that suggest that the "non-transmissible" status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the "natural" mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats that Chronic Wasting disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in

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Section: Alimentary Prion Infectionsmentioning

confidence: 65%

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

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Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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“…4) located at the cell surface and is soluble in the cytoplasm and in the nucleus. At the cell surface the protein serves as a receptor for a variety of substrates including: ECM components such as elastin and laminin; viruses including Sindbis 92 Dengue, 93 Venezuelan equine encephalitis and Adeno-associated virus subtypes 2, 3, 8 and 9, 31,32 as well as cellular 73 and infectious prion proteins 72,74,75 (Fig. 5).…”

Section: The 37 Kda/67 Kda Laminin Receptor Precursor/ Laminin Receptormentioning

confidence: 99%

“…PrP c constitutively cycles between the cell membrane and intra-cellular compartments via the endocytic pathway-a process mediated by the 37 kDa/67 kDa Laminin Receptor Precursor, 72 a high affinity receptor for PrP c73 and PrP Sc . 72,[74][75][76] The prion variants share a common amino acid sequence and differ primarily with regards to secondary structure (PrP Sc exhibits greater β sheet proportion than PrP c -consistent with its higher aggregation propensity) and proteinase K digestion (PrP Sc resists degradation while PrP c does not). 71,77 PrP c has a multitude of physiological functions 70 and the majority of these functions are dependent on the interaction of the prion protein with an array (>70)of proteins.…”

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confidence: 99%

Structural and mechanistic commonalities of amyloid-β and the prion protein

Dias

Jovanović

Gonsalves

et al. 2011

Prion

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Improvement of neuronal cell survival by astrocyte‐derived exosomes under hypoxic and ischemic conditions depends on prion protein

Guitart

Loers

Buck

et al. 2016

Glia

151

107

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Prion protein (PrP) protects neural cells against oxidative stress, hypoxia, ischemia, and hypoglycemia. In the present study we confirm that cultured PrP-deficient neurons are more sensitive to oxidative stress than wild-type neurons and present the novel findings that wild-type, but not PrP-deficient astrocytes protect wild-type cerebellar neurons against oxidative stress and that exosomes released from stressed wild-type, but not from stressed PrP-deficient astrocytes reduce neuronal cell death induced by oxidative stress. We show that neuroprotection by exosomes of stressed astrocytes depends on exosomal PrP but not on neuronal PrP and that astrocyte-derived exosomal PrP enters into neurons, suggesting neuronal uptake of astrocyte-derived exosomes. Upon exposure of wild-type astrocytes to hypoxic or ischemic conditions PrP levels in exosomes were increased. By mass spectrometry and Western blot analysis, we detected increased levels of 37/67 kDa laminin receptor, apolipoprotein E and the ribosomal proteins S3 and P0, and decreased levels of clusterin/apolipoprotein J in exosomes from wild-type astrocytes exposed to oxygen/glucose deprivation relative to exosomes from astrocytes maintained under normoxic conditions. The levels of these proteins were not altered in exosomes from stressed PrP-deficient astrocytes relative to unstressed PrP-deficient astrocytes. These results indicate that PrP in astrocytes is a sensor for oxidative stress and mediates beneficial cellular responses, e.g. release of exosomes carrying PrP and other molecules, resulting in improved survival of neurons under hypoxic and ischemic conditions.

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Prion Interaction with the 37-kDa/67-kDa Laminin Receptor on Enterocytes as a Cellular Model for Intestinal Uptake of Prions

Cited by 22 publications

References 40 publications

Alimentary prion infections

Alimentary prion infections

Structural and mechanistic commonalities of amyloid-β and the prion protein

Improvement of neuronal cell survival by astrocyte‐derived exosomes under hypoxic and ischemic conditions depends on prion protein

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