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Molecular basis of cerebral neurodegeneration in prion diseases
Author(s) -
Tatzelt Jörg,
Schätzl Hermann M.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05633.x
Subject(s) - neurodegeneration , gene isoform , prion protein , biology , function (biology) , scrapie , loss function , neuroscience , microbiology and biotechnology , amyloid (mycology) , transgene , fungal prion , disease , genetically modified mouse , phenotype , genetics , gene , medicine , pathology , botany
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.