In:
Journal of General Virology, Microbiology Society, Vol. 86, No. 6 ( 2005-06-01), p. 1861-1867
Abstract:
Transmissible spongiform encephalopathies are characterized by the accumulation of PrP Sc , a protease-resistant form of a host-derived protein termed PrP C . Substantial evidence indicates that PrP Sc represents an essential component of the infectious agent, which is termed prion. The accumulation of PrP Sc within the central nervous system of prion-infected organisms is a dynamic process that is regulated both by production and by clearance of PrP Sc . Although several proteases have been implicated in proteolysis of PrP C , the mechanisms underlying proteolysis of PrP Sc remain unclear. Here, it was investigated whether neprilysin, a metalloprotease known to degrade extracellular amyloidogenic proteins such as amyloid- β , 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 PrP Sc 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 PrP Sc accumulation and prion pathogenesis.
Type of Medium:
Online Resource
ISSN:
0022-1317
,
1465-2099
DOI:
10.1099/vir.0.80811-0
Language:
English
Publisher:
Microbiology Society
Publication Date:
2005
detail.hit.zdb_id:
2007065-2
SSG:
12
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