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Dissertation
Identifying genes that encode APP metabolism modulators on chromosome 9q22
Doctor of Philosophy (Ph.D.), Drexel University
Oct 2007
DOI:
https://doi.org/10.17918/etd-1876
Abstract
The central pathobiologic event in AD is regulated intramembrane proteolysis of the [beta]-amyloid precursor protein (APP), which generates the amyloidogenic [beta]-amyloid (A[beta]) peptide and the APP intracellular domain (AICD). The AICD fragment displays transcriptional activation properties. The genetic cause of AD is not fully accounted for by the known risk genes, and recent meta-analysis suggests that there are around 20 unidentified genes. Chromosome 9q22 is implicated to harbor AD genes by human genome scan results. Here I constructed an AICD-mediated functional assay to discover novel APP metabolism regulators. 11 positional candidate genes have been identified on this region and their functions are undergoing further characterization. I found that Ubiquilin 1 modulates APP metabolism and this function is cell type dependent. I also found that Ubiquilin 1 can modulate cell viability and its degradation requires proteasome and lysosome.
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Details
- Title
- Identifying genes that encode APP metabolism modulators on chromosome 9q22
- Creators
- Can Zhang - DU
- Contributors
- Aleister Saunders (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Bioscience and Biotechnology [Historical]; College of Arts and Sciences; Drexel University
- Other Identifier
- 1876; 991014632538704721