Inhibition of scrapie-associated PrP accumulation |
| |
Authors: | Suzette A Priola Byron Caughey |
| |
Institution: | (1) Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 59840 Hamilton, MT |
| |
Abstract: | Accumulation of an abnormal, protease-resistant form of an endogenous protein, PrP, is a characteristic feature of scrapie
and related transmissible spongiform encephalopathies. This abnormal isoform is also present in the amyloid plaques that are
often observed in these diseases. In mouse neuroblastoma cells persistently infected with scrapie, the abnormal protease-resistant
isoform of PrP is derived from an operationally normal protease-sensitive precursor. Conversion of PrP to the protease-resistant
state occurs either on the plasma membrane or along an endocytic pathway by an unknown mechanism. Inhibitors of protease-resistant
PrP accumulation have been identified, and these include the amyloid-binding dye Congo red and certain sulfated glycans. The
similarity of these compounds to sulfated glycosaminoglycans, which are components of all natural amyloids, has led to the
hypothesis that the inhibitors act by competitively blocking an interaction between endogenous glycosaminoglycan(s) and PrP
that is critical for amyloidogenic PrP accumulation. The proven prophylactic effect of these sulfated glycans in animal models
of scrapie suggests that they represent a group of compounds that might interfere with the pathogenic formation of amyloid
in a variety of diseases, such as Alzheimer's disease. |
| |
Keywords: | Scrapie PrP amyloid Congo red glycosaminoglycans Alzheimer's disease |
本文献已被 SpringerLink 等数据库收录! |
|