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P1–392: Oxysterol crosstalk at the blood–brain barrier
Author(s) -
Heverin Maura B.,
Axelson Magnus,
Meaney Steve,
Diczfalusy Ulf,
Wahren John,
Björkhem Ingemar
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.770
Subject(s) - oxysterol , cholesterol , medicine , cyp27a1 , endocrinology , human brain , chemistry , biology , neuroscience
HPLC analysis and/or densitometric analysis of peptides separated by SDS-PAGE. Results: Each protease was capable of degrading both wt and mutant (aggregate-free) synthetic and cell-derived A peptides. Moreover, experiments investigating the rates of cleavage of synthetic A peptides revealed that all peptides are degraded similarly by IDE and plasmin, but that the Flemish peptide was degraded significantly more slowly by NEP than wt or other mutant peptides. Importantly, we show that the ability of these proteases to degrade A is strongly retarded by aggregation. However, the decreased proteolysis of the G21 peptide by NEP cannot be attributed to its aggregation state as we also find that the G21 peptide aggregates less readily than the WT peptide. Conclusions: The resistance of the G21 peptide to proteolysis by NEP may represent one mechanism by which this mutation causes increased intracerebral accumulation of A .