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Increasing neurite outgrowth capacity of β‐amyloid precursor protein proteoglycan in Alzheimer's disease
Author(s) -
Salinero Olga,
MorenoFlores M. Teresa,
Wandosell Francisco
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000401)60:1<87::aid-jnr9>3.0.co;2-c
Subject(s) - neurite , senile plaques , amyloid precursor protein , p3 peptide , laminin , hippocampal formation , population , microbiology and biotechnology , biochemistry of alzheimer's disease , alzheimer's disease , neuroscience , biology , proteoglycan , human brain , biochemistry , extracellular matrix , medicine , in vitro , disease , environmental health
Progressive cerebral deposition of β‐amyloid peptide either in blood vessels or around neurites is one of the most important features of Alzheimer's disease (AD). The β‐peptide, known as Aβ or A4, is produced by proteolytic cleavage of the amyloid precursor protein (APP). Two APP processing pathways have been proposed as physiological alternatives; only one of which leads to the production of Aβ or amyloidogenic peptides. However, we have little information regarding these processing pathways in the brain, or on whether posttranslational modifications such as glycosylation affect APP processing in vivo. Furthermore, the physiological function(s) of this protein in nervous tissue remains unclear, although modulatory roles in cell adhesion and neuritic extension have been suggested. It has been reported that APP may be glycosylated as a proteoglycan. We purified this APP population from human brain, and our data indicate that PG‐APP supports neurite extension of hippocampal neurons. Neurons grown on this substratum showed an increased capacity to elongate neurites and increased neuritic “branching” compared to culture on laminin. These effects were enhanced with PG‐APP samples obtained from AD brains. Our results suggest that this APP population may act as a neurite outgrowth and branching promoter and may thus play a role in some pathological conditions. These findings may have significant implications in understanding normal brain development and pathological situations (such as AD). J. Neurosci. Res. 60:87–97, 2000 © 2000 Wiley‐Liss, Inc.