Abstract
At the endoplasmic reticulum membrane, the prion protein (PrP) can be synthesized in several topological forms. The role of these different forms was explored with transgenic mice expressing PrP mutations that alter the relative ratios of the topological forms. Expression of a particular transmembrane form (termed CtmPrP) produced neurodegenerative changes in mice similar to those of some genetic prion diseases. Brains from these mice contained CtmPrP but not PrPSc, the PrP isoform responsible for transmission of prion diseases. Furthermore, in one heritable prion disease of humans, brain tissue contained CtmPrP but not PrPSc. Thus, aberrant regulation of protein biogenesis and topology at the endoplasmic reticulum can result in neurodegeneration.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Brain / metabolism
-
Brain / pathology
-
Cricetinae
-
Endopeptidases / metabolism
-
Endoplasmic Reticulum / chemistry
-
Endoplasmic Reticulum / metabolism*
-
Gerstmann-Straussler-Scheinker Disease / metabolism
-
Humans
-
Intracellular Membranes / chemistry
-
Mesocricetus
-
Mice
-
Mice, Transgenic
-
Molecular Sequence Data
-
Mutation
-
Neurodegenerative Diseases / etiology*
-
Neurodegenerative Diseases / metabolism
-
Neurodegenerative Diseases / pathology
-
PrPC Proteins / biosynthesis
-
PrPC Proteins / chemistry*
-
PrPC Proteins / genetics
-
PrPC Proteins / metabolism*
-
PrPSc Proteins / chemistry
-
PrPSc Proteins / metabolism
-
Prion Diseases / etiology
-
Prion Diseases / metabolism
-
Prion Diseases / pathology
-
Prions / biosynthesis
-
Prions / chemistry*
-
Prions / genetics
-
Prions / metabolism*
-
Protein Conformation
Substances
-
(ctm)PrP
-
PrPC Proteins
-
PrPSc Proteins
-
Prions
-
Endopeptidases