Kinetics of prion growth

被引:65
作者
Pöschel, T [1 ]
Brilliantov, NV [1 ]
Frömmel, C [1 ]
机构
[1] Humboldt Univ, Inst Biochem, Charite, Berlin, Germany
关键词
D O I
10.1016/S0006-3495(03)74767-5
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
We study the kinetics of prion fibril growth, described by the nucleated polymerization model analytically and by means of numerical experiments. The elementary processes of prion fibril formation lead us to a set of differential equations for the number of fibrils, their total mass, and the number of prion monomers. In difference to previous studies we analyze this set by explicitly taking into account the time-dependence of the prion monomer concentration. The theoretical results agree with experimental data, whereas the generally accepted hypothesis of constant monomer concentration leads to a fibril growth behavior which is not in agreement with experiments. The obtained size distribution of the prion fibril aggregates is shifted significantly toward shorter lengths as compared to earlier results, which leads to a enhanced infectivity of the prion material. Finally, we study the effect of filtering of the inoculated material on the incubation time of the disease.
引用
收藏
页码:3460 / 3474
页数:15
相关论文
共 32 条
[1]   DOES AGENT OF SCRAPIE REPLICATE WITHOUT NUCLEIC ACID [J].
ALPER, T ;
CRAMP, WA ;
HAIG, DA ;
CLARKE, MC .
NATURE, 1967, 214 (5090) :764-&
[2]  
[Anonymous], PRION BIOL DIS
[3]   Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie [J].
Beekes, M ;
Baldauf, E ;
Diringer, H .
JOURNAL OF GENERAL VIROLOGY, 1996, 77 :1925-1934
[4]  
Bender C.M., 1978, Advanced mathematical methods for scientists and engineers
[5]  
BUELER H, 1994, MOL MED, V1, P19
[6]   STRUCTURAL CLUES TO PRION REPLICATION [J].
COHEN, FE ;
PAN, KM ;
HUANG, Z ;
BALDWIN, M ;
FLETTERICK, RJ ;
PRUSINER, SB .
SCIENCE, 1994, 264 (5158) :530-531
[7]   Prionics or The kinetic basis of prion diseases [J].
Eigen, M .
BIOPHYSICAL CHEMISTRY, 1996, 63 (01) :A1-A18
[8]  
FEISTEL R, 1976, THESIS W PIECK U ROS
[9]  
FEISTEL R, 1977, WISS Z U ROSTOCK, V26, P663
[10]   GENERAL METHOD FOR NUMERICALLY SIMULATING STOCHASTIC TIME EVOLUTION OF COUPLED CHEMICAL-REACTIONS [J].
GILLESPIE, DT .
JOURNAL OF COMPUTATIONAL PHYSICS, 1976, 22 (04) :403-434