Differenzielle Effekte von Presenilin-Mutationen auf die Generierung des Amyloid-ß-Peptids (Aß) und die Endoproteolyse des Notch-Rezeptors
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vor 20 Jahren
Most of the genetically inherited Alzheimer's disease cases are
caused by mutations in the presenilin genes, PS1 and PS2. PS
mutations result in the enhanced production of the highly
amyloidogenic 42/43 amino acid variant of amyloid ß-peptide (Aß).
Arbitrary mutations were introduced at position 286 of PS1, where a
naturally occurring PS1 mutation has been described (L286V).
Introduction of charged amino acids (L286E or L286R) resulted in an
increase of Aß42/43 production, which reached almost twice the
level of the naturally occurring PS1 mutation. Although
pathological Aß production was increased, endoproteolysis of Notch
and nuclear transport of its cytoplasmic domain was significantly
inhibited. These results demonstrate differential effects of PS
proteins in the endoproteolysis of the ß-amyloid precursor protein
and Notch.
caused by mutations in the presenilin genes, PS1 and PS2. PS
mutations result in the enhanced production of the highly
amyloidogenic 42/43 amino acid variant of amyloid ß-peptide (Aß).
Arbitrary mutations were introduced at position 286 of PS1, where a
naturally occurring PS1 mutation has been described (L286V).
Introduction of charged amino acids (L286E or L286R) resulted in an
increase of Aß42/43 production, which reached almost twice the
level of the naturally occurring PS1 mutation. Although
pathological Aß production was increased, endoproteolysis of Notch
and nuclear transport of its cytoplasmic domain was significantly
inhibited. These results demonstrate differential effects of PS
proteins in the endoproteolysis of the ß-amyloid precursor protein
and Notch.
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