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.
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.
|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
|Date:||1 June 2005|
|Deposited On:||11 Feb 2008 12:25|
|Last Modified:||27 Nov 2013 19:49|
|Publisher:||Society for General Microbiology|
|Citations:||Web of Science®. Times Cited: 4|
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