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Updated: May 20, 2026
07:17
Purification of Hsp104, a Protein Disaggregase
Published on: September 30, 2011
Prion protein expression alters APP cleavage without interaction with BACE-1.
Patrick C McHugh1, Josephine A Wright, Robert J Williams
1Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Neurochemistry International
|July 17, 2012
Summary
Prion protein (PrP) and BACE-1 do not directly interact. Altered PrP expression impacts BACE-1 levels and amyloid precursor protein (APP) cleavage, suggesting an indirect relationship possibly linked to copper metabolism.
Area of Science:
- Neurodegenerative diseases
- Molecular biology
- Biochemistry
Background:
- Prion protein (PrP) and BACE-1 are copper-binding proteins implicated in distinct neurodegenerative diseases.
- BACE-1's role in beta-amyloid formation makes it a therapeutic target for Alzheimer's disease.
- A potential interaction between PrP and BACE-1 influencing Alzheimer's disease pathogenesis was proposed.
Purpose of the Study:
- To investigate the physical and molecular interactions between PrP and BACE-1.
- To determine the effect of PrP on BACE-1 activity and amyloid precursor protein (APP) cleavage.
- To elucidate the relationship between PrP and BACE-1 in the context of neurodegeneration.
Main Methods:
- Investigated physical interaction between PrP and BACE-1.
- Assessed transcriptional and translational regulation of BACE-1.
- Quantified APP cleavage in response to altered PrP expression.
Main Results:
- Mature PrP and BACE-1 do not physically interact.
- Altered PrP expression affects BACE-1 protein levels and promoter activity.
- Overexpression of PrP increases APP cleavage, contrary to previous findings.
Conclusions:
- The relationship between PrP and BACE-1 is indirect.
- Altered PrP expression influences BACE-1 and APP processing.
- Changes in copper metabolism may mediate the effects of PrP expression alterations.
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