tailieunhanh - Báo cáo khoa học: Molecular basis of cerebral neurodegeneration in prion diseases

The biochemical nature and the replication of infectious prions have been intensively studied in recent years. Much less is known about the cellular events underlying neuronal dysfunction and cell death. As the cellular func-tion of the normal cellular isoform of prion protein is not exactly known, the impact of gain of toxic function or loss of function, or a combination of both, in prion pathology is still controversial. | MINIREVIEW Molecular basis of cerebral neurodegeneration in prion diseases Jorg Tatzelt1 and Hermann M. Schatzl2 1 Department of Biochemistry Neurobiochemistry Ludwig-Maximilians-University Munich Germany 2 Institute of Virology TechnicalUniversity of Munich Germany Keywords amyloid neurodegeneration prion protein prion trafficking transmissibility Correspondence J. Tatzelt Department of Biochemistry Ludwig-Maximilians-University Munich Schillerstrasse 44 80336 Munich Germany Fax 49 89 2180 75415 Tel 49 89 2180 75442 E-mail H. M. Schatzl Institute of Virology TechnicalUniversity Munich TUM TrogerstraBe 30 81675 Munich Germany Fax 49 89 4140 6823 Tel 49 89 4140 6820 E-mail schaetzl@ Received 2 August 2006 revised 30 November 2006 accepted 4 December 2006 doi The biochemical nature and the replication of infectious prions have been intensively studied in recent years. Much less is known about the cellular events underlying neuronal dysfunction and cell death. As the cellular function of the normal cellular isoform of prion protein is not exactly known the impact of gain of toxic function or loss of function or a combination of both in prion pathology is still controversial. There is increasing evidence that the normal cellular isoform of the prion protein is a key mediator in prion pathology. Transgenic models were instrumental in dissecting propagation of prions disease-associated isoforms of prion protein and amyloid production and induction of neurodegeneration. Four experimental avenues will be discussed here which address scenarios of inappropriate trafficking folding or targeting of the prion protein. Prion diseases in their classical and naturally occurring forms are characterized by both neurodegeneration with clinical symptoms and propagation of infectious prions the latter giving rise to the typical transmissibility within and between species 1-5 . The formation of the .