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Nε-Carboxymethyl Modification of Lysine Residues in Pathogenic Prion Isoforms
- Source :
- Molecular Neurobiology
- Publisher :
- Springer Nature
-
Abstract
- The most prominent hallmark of prion diseases is prion protein conversion and the subsequent deposition of the altered prions, PrPSc, at the pathological sites of affected individuals, particularly in the brain. A previous study has demonstrated that the N-terminus of the pathogenic prion isoform (PrPSc) is modified with advanced glycation end products (AGEs), most likely at one or more of the three Lys residues (positions 23, 24, and 27) in the N-terminus (23KKRPKP28). The current study investigated whether Nε-(carboxymethyl)lysine (CML), a major AGE form specific to Lys residues produced by nonenzymatic glycation, is an AGE adduct of the N-terminus of PrPSc. We show that CML is linked to at least one Lys residue at the N-terminus of PrPSc in 263K prion-infected hamster brains and at least one of the eight Lys residues (positions 101, 104, 106, 110, 185, 194, 204, and 220) in the proteinase K (PK)-resistant core region of PrPSc. The nonenzymatic glycation of the Lys residue(s) of PrPSc with CML likely occurs in the widespread prion-deposit areas within infected brains, particularly in some of the numerous tyrosine hydroxylase-positive thalamic and hypothalamic nuclei. CML glycation does not occur in PrPC but is seen in the pathologic PrPSc isoform. Furthermore, the modification of PrPSc with CML may be closely involved in prion propagation and deposition in pathological brain areas. Electronic supplementary material The online version of this article (doi:10.1007/s12035-015-9200-8) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Gene isoform
Glycation End Products, Advanced
Male
Glycosylation
PrPSc Proteins
Tyrosine 3-Monooxygenase
Prions
animal diseases
Lysine
Neuroscience (miscellaneous)
Prion disease
Article
03 medical and health sciences
chemistry.chemical_compound
Cellular and Molecular Neuroscience
Thalamus
Glycation
Animals
Protein Isoforms
Tyrosine
Advanced glycation end products
Neurons
biology
Mesocricetus
Nε-(carboxymethyl)lysine
Cell Membrane
Proteinase K
biology.organism_classification
263K
Cell Compartmentation
nervous system diseases
030104 developmental biology
Neurology
chemistry
Biochemistry
Solubility
biology.protein
Endopeptidase K
Subjects
Details
- Language :
- English
- ISSN :
- 08937648
- Volume :
- 53
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....bb658279b8a404d428bb7e713e27c3a6
- Full Text :
- https://doi.org/10.1007/s12035-015-9200-8