Amyloid precursor protein proteoglycan is increased after brain damage.
The beta-amyloid peptide (Abeta or A4) is produced by proteolytic cleavage from amyloid precursor protein (APP). The progressive cerebral deposition of this peptide is one of the most important features of Alzheimer's disease. From the study of normal and transfected cells, two APP processing pathways have been proposed as physiological alternatives. One of these can produce Abeta or amyloidogenic peptides, whereas the second does not. However, it is not completely clear how APPs are post-translationally modified, proteolytically processed and metabolized in the brain. We report here that APPs also exist as proteoglycan, chondroitin-sulfate (ChS). We have identified in normal rat brain a complex pool of 8 to 130 kDa ChS-core proteins. The main portion of these proteoglycan (PGs) APPs contains complete amyloidogenic sequence, suggesting a novel proteolytic processing of APP from the amino-terminal to the transmembrane region. This population appears augmented after brain damage. These findings may have significant implications in understanding the initial deposition and kinetics of amyloid aggregation in a pathological situation like Alzheimer's disease.
Salinero
O
O
Centro de Biología Molecular 'Severo Ochoa', CSIC-Universidad Autonoma de Madrid, Cantoblanco-Madrid 28049, Spain.
Garrido
J J
JJ
Wandosell
F
F
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D007106:Immune Sera / Q000737:chemistry / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
D016564:Amyloid beta-Protein Precursor; D011508:Chondroitin Sulfate Proteoglycans; D007106:Immune Sera; D007074:Immunoglobulin G; D010446:Peptide Fragments; D007608:Kainic Acid