Regional phenotypes of cellular prion proteins in human brains identified by differential detergent solubility

Abstract A hallmark of prion diseases is the accumulation of disease-associated isoforms (PrPSc ) which results from the conversion of host-encoded cellular prion proteins (PrPC ). Using molecular biochemistry, several disease variants of the human Creutzfeldt–Jakob disease have been identified show...

Full description

Saved in:

Bibliographic Details
Published in:	Brain research 2013-04, Vol.1507, p.19-27
Main Authors:	Kuczius, Thorsten, Groschup, Martin H
Format:	Article
Language:	eng
Subjects:	Adult Aged Biological and medical sciences Brain Chemistry Cellular prion protein PrPC cerebellum Creutzfeldt-Jakob Syndrome Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases deoxycholic acid Detergents Differential protein solubility Differential PrPC composition Female gene expression regulation Glycoprotein typing glycoproteins Glycoproteins - analysis hippocampus Human brain regions Humans Male Medical sciences medulla oblongata Middle Aged neocortex Neurology phenotype prions PrPC Proteins - analysis PrPC Proteins - chemistry PrPC Proteins - classification sediments Solubility thalamus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract A hallmark of prion diseases is the accumulation of disease-associated isoforms (PrPSc ) which results from the conversion of host-encoded cellular prion proteins (PrPC ). Using molecular biochemistry, several disease variants of the human Creutzfeldt–Jakob disease have been identified showing several PrPSc variants in individuals and selective accumulation in specific brain regions. As PrPC is differentially expressed and post-translationally modified, certain distinct protein compositions may have the ability to convert more efficiently than others. The PrPC glycoprotein moiety represents a single yet divers mixture, but little is known about its exact composition. In this study, we separated and characterized PrPC derived from six defined human brain regions in regard to their solubility in several detergent solutions and glycoprotein profile formation. We identified four different but regionally distinct protein compositions. PrPC found in the neocortex exhibited dominant diglycosylated bands in the high as well as in the low soluble fractions. The proteins in the nucleus lentiformis, thalamus and hippocampus were more soluble with deoxycholic acid as the N -octyl-β- d -glucopyranoside and the diglycosylated bands displayed strong signals in the supernatants and weaker signals in the sediments. Two different protein profiles were established with PrPC derived from the medulla oblongata and the solubility of PrPC in the cerebellum clearly differed by the choice of detergent. Our findings indicate the existence of several distinct PrPC compositions localized in distinct brain regions. Protein variations may be induced by specific modifications to specific regional biological functions.
ISSN:	0006-8993 1872-6240