Tschape, Jakob-Andreas and Hammerschmied, Christine and Muehlig-Versen, Max and Athenstaedt, Karin and Daum, Günther and Kretzschmar, Doris (2002) The neurodegeneration mutant lochrig interferes with cholesterol homeostasis and Appl processing. EMBO JOURNAL, 21 (23). pp. 6367-6376. ISSN 0261-4189
Full text not available from this repository. (Request a copy)Abstract
The novel Drosophila mutant lochrig (loe) shows progressive neurodegeneration and neuronal cell death, in addition to a low level of cholesterol ester. loe affects a specific isoform of the gamma-subunit of AMP-activated protein kinase (AMPK), a negative regulator of hydroxymethylglutaryl (HMG)-CoA reductase and cholesterol synthesis in vertebrates. Although Drosophila cannot synthesize cholesterol de novo, the regulatory role of fly AMPK on HMG-CoA reductase is conserved. The loe phenotype is modified by the level of HMG-CoA reductase and suppressed by the inhibition of this enzyme by statin, which has been used for the treatment of Alzheimer patients. In addition, the degenerative phenotype of loe is enhanced by a mutation in amyloid precursor protein-like (APPL), the fly homolog of the human amyloid precursor protein involved in Alzheimer's disease. Western analysis revealed that the loe mutation reduces APPL processing, whereas overexpression of Loe increases it. These results describe a novel function of AMPK in neurodegeneration and APPL/APP processing which could be mediated through HMG-CoA reductase and cholesterol ester.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE; AMYLOID PRECURSOR PROTEIN; COENZYME-A REDUCTASE; HUMAN APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; DROSOPHILA-MELANOGASTER; BETA-PEPTIDE; CELL; GENE; IDENTIFICATION; amyloid precursor protein-like; cholesterol; Drosophila; neurodegeneration |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Sep 2021 09:11 |
| Last Modified: | 28 Sep 2021 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39571 |
Actions (login required)
 |
View Item |
