Experimental approaches to the interaction of the prion protein with nucleic acids and glycosaminoglycans: Modulators of the pathogenic conversion

被引:22
作者
Silva, Jerson L. [1 ]
Vieira, Tuane C. R. G.
Gomes, Mariana P. B.
Rangel, Luciana P.
Scapin, Sandra M. N.
Cordeiro, Yraima [1 ]
机构
[1] Univ Fed Rio de Janeiro, Inst Bioquim, Fac Farm, BR-21941590 Rio De Janeiro, Brazil
关键词
Prion protein; PrP; Nucleic acids; Glycosaminoglycans; Transmissible spongiform; Encephalopathy; Neurodegenerative diseases; PrP partners; PrP structure; PrP conversion; CREUTZFELDT-JAKOB-DISEASE; LAMININ RECEPTOR ACTS; BETA-SHEET CONVERSION; CLATHRIN-COATED PITS; N-TERMINAL DOMAIN; SCRAPIE PRION; NEUROBLASTOMA-CELLS; BINDING-SITES; IN-VITRO; MAMMALIAN PRIONS;
D O I
10.1016/j.ymeth.2010.12.002
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The concept that transmissible spongiform encephalopathies (TSEs) are caused only by proteins has changed the traditional paradigm that disease transmission is due solely to an agent that carries genetic information. The central hypothesis for prion diseases proposes that the conversion of a cellular prion protein (PrPC) into a misfolded, beta-sheet-rich isoform (PrPSc) accounts for the development of (TSE). There is substantial evidence that the infectious material consists chiefly of a protein, PrPSc, with no genomic coding material, unlike a virus particle, which has both. However, prions seem to have other partners that chaperone their activities in converting the PrPC into the disease-causing isoform. Nucleic acids (NAs) and glycosaminoglycans (GAGs) are the most probable accomplices of prion conversion. Here, we review the recent experimental approaches that have been employed to characterize the interaction of prion proteins with nucleic acids and glycosaminoglycans. A PrP recognizes many nucleic acids and GAGs with high affinities, and this seems to be related to a pathophysiological role for this interaction. A PrP binds nucleic acids and GAGs with structural selectivity, and some PrP:NA complexes can become proteinase K-resistant, undergoing amyloid oligomerization and conversion to a beta-sheet-rich structure. These results are consistent with the hypothesis that endogenous polyanions (such as NAs and GAGS) may accelerate the rate of prion disease progression by acting as scaffolds or lattices that mediate the interaction between PrPC and PrPSc molecules. In addition to a still-possible hypothesis that nucleic acids and GAGs, especially those from the host, may modulate the conversion, the recent structural characterization of the complexes has raised the possibility of developing new diagnostic and therapeutic strategies. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:306 / 317
页数:12
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