Differenzielle Effekte von Presenilin-Mutationen auf die Generierung des Amyloid-ß-Peptids (Aß) und die Endoproteolyse des Notch-Rezeptors

Abstract

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.

• Item Type: Thesis (Dissertation, LMU Munich)
• Keywords: Presenilin, Notch, Aß, gamma-Sekretase, Alzheimer
• Dewey Decimal Classification: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: German
• Date Accepted: 31. July 2003
• Persistent Identifier (URN): urn:nbn:de:bvb:19-12409
• Signature of the printed copy: 0700/UMD 10214