The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing

Jakob Andreas Tschäpe, Christine Hammerschmied, Max Mühlig-Versen, Karin Athenstaedt, Günther Daum, Doris Kretzschmar

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The novel Drosophila mutant löchrig (loe) shows progressive neurodegeneration and neuronal cell death, in addition to a low level of cholesterol ester. loe affects a specific isoform of the γ-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.

Original languageEnglish (US)
Pages (from-to)6367-6376
Number of pages10
JournalEMBO Journal
Volume21
Issue number23
DOIs
StatePublished - Dec 2 2002
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl CoA Reductases
Amyloid beta-Protein Precursor
AMP-Activated Protein Kinases
Homeostasis
Cholesterol
Cholesterol Esters
Processing
Diptera
Drosophila
Phenotype
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mutation
Cell death
Vertebrates
Alzheimer Disease
Protein Isoforms
Cell Death
Enzymes

Keywords

  • Amyloid precursor protein-like
  • Cholesterol
  • Drosophila
  • Neurodegeneration

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Tschäpe, J. A., Hammerschmied, C., Mühlig-Versen, M., Athenstaedt, K., Daum, G., & Kretzschmar, D. (2002). The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. EMBO Journal, 21(23), 6367-6376. https://doi.org/10.1093/emboj/cdf636

The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. / Tschäpe, Jakob Andreas; Hammerschmied, Christine; Mühlig-Versen, Max; Athenstaedt, Karin; Daum, Günther; Kretzschmar, Doris.

In: EMBO Journal, Vol. 21, No. 23, 02.12.2002, p. 6367-6376.

Research output: Contribution to journalArticle

Tschäpe, JA, Hammerschmied, C, Mühlig-Versen, M, Athenstaedt, K, Daum, G & Kretzschmar, D 2002, 'The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing', EMBO Journal, vol. 21, no. 23, pp. 6367-6376. https://doi.org/10.1093/emboj/cdf636
Tschäpe, Jakob Andreas ; Hammerschmied, Christine ; Mühlig-Versen, Max ; Athenstaedt, Karin ; Daum, Günther ; Kretzschmar, Doris. / The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. In: EMBO Journal. 2002 ; Vol. 21, No. 23. pp. 6367-6376.
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