Targeting prion proteins in neurodegenerative disease.
BACKGROUND
Spongiform neurodegeneration is the pathological hallmark of individuals suffering from prion disease. These disorders, whose manifestation is sporadic, familial or acquired by infection, are caused by accumulation of the aberrantly folded isoform of the cellular prion protein (PrP(c)), termed PrP(Sc). Although usually rare, prion disorders are inevitably fatal and transferrable by infection.


OBJECTIVE
Pathology is restricted to the central nervous system and premortem diagnosis is usually not possible. Yet, promising approaches towards developing therapeutic regimens have been made recently.


METHODS
The biology of prion proteins and current models of neurotoxicity are discussed and prophylactic and therapeutic concepts are introduced.


CONCLUSIONS
Although various promising drug candidates with antiprion activity have been identified, this proof-of-concept cannot be transferred into translational medicine yet.
Gilch
Sabine
S
Technische Universität München, Institute of Virology, Prion Research Group, Trogerstreet 30, 81675 Munich, Germany.
Krammer
Carmen
C
Schätzl
Hermann M
HM
D000818:Animals; D001695:Biology / Q000379:methods; D007562:Creutzfeldt-Jakob Syndrome / Q000628:therapy; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry; D017096:Prion Diseases / Q000628:therapy; D011328:Prions / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms