Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1783

Glatzel, M; Mohajeri, M H; Poirier, R; Nitsch, R M; Schwarz, Petra; Lu, B; Aguzzi, A (2005). No influence of amyloid-beta-degrading neprilysin activity on prion pathogenesis. Journal of General Virology, 8(6):1861-1867.

[img]
Preview
PDF
428kB

View at publisher

Abstract

Transmissible spongiform encephalopathies are characterized by the accumulation of PrPSc, a protease-resistant form of a host-derived protein termed PrPC. Substantial evidence indicates that PrPSc represents an essential component of the infectious agent, which is termed prion. The accumulation of PrPSc within the central nervous system of prion-infected organisms is a dynamic process that is regulated both by production and by clearance of PrPSc. Although several proteases have been implicated in proteolysis of PrPC, the mechanisms underlying proteolysis of PrPSc remain unclear. Here, it was investigated whether neprilysin, a metalloprotease known to degrade extracellular amyloidogenic proteins such as amyloid-beta, plays a role in prion pathogenesis in vivo. As neprilysin has a broad substrate specificity and is localized subcellularly in the vicinity of PrP, it represents a plausible candidate for prion degradation. Prions were therefore administered to mice lacking or overexpressing neprilysin in brain. However, the gene dosage of neprilysin did not modulate accumulation of PrPSc in brain. Also, incubation times and clinical course of prion disease, as well as brain infectivity titres at terminal stage, were unaffected. These data rule out neprilysin as a major modulator of PrPSc accumulation and prion pathogenesis.

Citations

Altmetrics

Downloads

100 downloads since deposited on 11 Feb 2008
59 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 June 2005
Deposited On:11 Feb 2008 12:25
Last Modified:27 Nov 2013 19:49
Publisher:Society for General Microbiology
ISSN:0022-1317
Publisher DOI:10.1099/vir.0.80811-0
PubMed ID:15914866

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page