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Publication Review:Pathogenesis of Transmissible Spongiform Encephalopathies in ...  

Update Date: [2013-11-13]

NO.: 37
 
Reportno.

AHRI report No.37

Topic

Review:Pathogenesis of Transmissible Spongiform Encephalopathies in Molecular Biology Aspects

 

Department

Animal Health Research Institute, Council of Agriculture

Author Shu-Hwae LEE, Kuo-Hui CHAN Ming-Hwa JON Shth-Yuh LIN
Summary

SUMMARY Transmissible spongiform ncephalopathies (TSEs) are often propi,gati by extracerehal inoculation. The mhanisn of spread from eripherai portals of entry to the central nervous system (neuroinvasion) is complex While lymphatic organs show early accumulation of prions, B-cells and follicular daidritic cells axe rezpiired for efficient neuroinvasion. Intact pxions enter the central nervous system probably via rerirtheral nerves and may need a cellular counterpart of gion got (PrPQ for propagation. TSES axe chaxacterizid by accumulating an abnormal isoforru (PrPSc) of the host-esmied PrPC in brain, la 1982. Prusiner firstly purified the infeztious agent from hamster ham and intrcduced the term “prion” for goteinacsc’us infectious particle. The PrP isoforms contain identical amino-acid serpience., yet differ in their overall secondary stricture with the PrPSc isoform, possess a higher fl-sheet and lower a-helix content than PrPC. In 1%?, Griffith SIUDJUar7 suggestl that & poGsible cause of scxapie may baa self replicaujig got. Consequently, by a series of excerimenis, Prusiner et al demonstrati that the infectivity was increased when a sfic got was contained in the sample. In the other words, the infectivity correlated closely with the concentration of the got. Acx:ording to these results, Prusiner goposed and developed the “got-only” hypothesis. Weissmann et al. cloned and sequenced the host PrP gene, which enosdes for PrEC. By unknown mechanisms, an autccatalytic cycle was probably initiated by infrcdwDing exogenous PrPSc, and resultei in the conversion of?-helix intofi-shet conformation. Unlike the ?-helical PrPC, the gotease-resistant core of PrPSc is predominantly ?-sheet and pcxssesses a tendency to polymerize into amyloid fihils. Nevertheless, the molecular mechanism of the conformation rearrar*gement of PrPC into PrPSc is still unknown.

 

Keyword

PrPSc-?rP isoforms; neuroinvasion.