{"id":{"repo_id":"lmu-germany","oai_identifier":"oai:edoc.ub.uni-muenchen.de:1240"},"canonical_url":"https://search.dev.ndltd.org/etd/lmu-germany/oai:edoc.ub.uni-muenchen.de:1240","repository":{"repo_id":"lmu-germany","name":"Ludwig Maxmilians Universität München","base_url":"https://edoc.ub.uni-muenchen.de/cgi/oai2"},"display":{"title":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Kulic, Luka"],"institution":"Ludwig-Maximilians-Universität","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003-07-31","date_published":"2003-07-31","updated_at":"2026-07-24T02:51:44Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://edoc.ub.uni-muenchen.de/1240/","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Kulic, Luka"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek der Ludwig-Maximilians-Universität"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Ludwig-Maximilians-Universität"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Differenzielle Effekte von Presenilin-Mutationen auf die Generierung des Amyloid-ß-Peptids (Aß) und die Endoproteolyse des Notch-Rezeptors"]}]}],"canonical_facts":{"dc:creator":["Kulic, Luka"],"dc:description.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."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek der Ludwig-Maximilians-Universität"],"dc:title":["Differenzielle Effekte von Presenilin-Mutationen auf die Generierung des Amyloid-ß-Peptids (Aß) und die Endoproteolyse des Notch-Rezeptors"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Ludwig-Maximilians-Universität"]},"updated_at":"2026-07-24T02:51:44Z"}