Advanced glycation modification of Rosenthal fibers in patients with Alexander disease.
Rosenthal fibers, astrocytic inclusions that accumulate in various neoplastic and non-neoplastic conditions, are a characteristic of Alexander disease, a leukodystrophy of unknown etiology. Given that alphaB crystallin is the major protein component of Rosenthal fibers and that crystallins in the diabetic and aged lens are targets for advanced glycation end product modifications via the Maillard reaction we hypothesized that Rosenthal fibers might contain similar modifications. Using antibodies specific for two products of glycation, pyrraline and pentosidine, we showed labeling of Rosenthal fibers that may account for their insolubility and accumulation. These data suggest that advanced glycation end products may be critical to the pathogenesis of Alexander disease.
Castellani
R J
RJ
Department of Pathology, University of Maryland Medical System, Baltimore 21201-1595, USA.
Perry
G
G
Harris
P L
PL
Monnier
V M
VM
Cohen
M L
ML
Smith
M A
MA
D000293:Adolescent; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology*; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D002648:Child; D003432:Cross-Linking Reagents / Q000032:analysis; D003459:Crystallins / Q000032:analysis; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D009646:Norleucine / Q000031:analogs & derivatives / Q000032:analysis; D011758:Pyrroles / Q000032:analysis
D003432:Cross-Linking Reagents; D003459:Crystallins; D017127:Glycation End Products, Advanced; D011758:Pyrroles; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D001120:Arginine; C062187:pentosidine; D008239:Lysine