Prion protein expression alters APP cleavage without interaction with BACE-1

Patrick C McHugh, Josephine A Wright, Robert J Williams, David R Brown

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The prion protein (PrP) and the beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE-1) are both copper binding proteins, but are associated with two separate neurodegenerative diseases. The role of BACE-1 in the formation of beta-amyloid has made it a major target in attempts to reduce the formation of beta-amyloid in Alzheimer's diseases. However, the suggestion that PrP, normally associated with prion diseases, binds to BACE-1 and reduces its activity has led to the suggestion that the study of this interaction could be of considerable importance to Alzheimer's disease. We therefore undertook to investigate the possible interaction of these two proteins physically and at the level of transcription, translation and APP cleavage. Our findings suggest that mature PrP and BACE-1 do not physically interact, but that altered PrP expression results in altered BACE-1 protein expression and promoter activity. Additionally, overexpression of PrP results in increased cleavage of APP in contrast to previous datas suggesting a reduction. Our findings suggest that any relation between PrP and BACE-1 is indirect. Altered expression of PrP causes changes in the expression of many other proteins which may be as a result of altered copper metabolism.

Original languageEnglish
Pages (from-to)672-680
Number of pages9
JournalNeurochemistry International
Volume61
Issue number5
Early online date10 Jul 2012
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

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Amyloid beta-Protein Precursor
Amyloid
Alzheimer Disease
Proteins
Prion Diseases
Prion Proteins
Neurodegenerative Diseases
Copper
Enzymes

Cite this

McHugh, Patrick C ; Wright, Josephine A ; Williams, Robert J ; Brown, David R. / Prion protein expression alters APP cleavage without interaction with BACE-1. In: Neurochemistry International. 2012 ; Vol. 61, No. 5. pp. 672-680.
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Prion protein expression alters APP cleavage without interaction with BACE-1. / McHugh, Patrick C; Wright, Josephine A; Williams, Robert J; Brown, David R.

In: Neurochemistry International, Vol. 61, No. 5, 10.2012, p. 672-680.

Research output: Contribution to journalArticle

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AU - McHugh, Patrick C

AU - Wright, Josephine A

AU - Williams, Robert J

AU - Brown, David R

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AB - The prion protein (PrP) and the beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE-1) are both copper binding proteins, but are associated with two separate neurodegenerative diseases. The role of BACE-1 in the formation of beta-amyloid has made it a major target in attempts to reduce the formation of beta-amyloid in Alzheimer's diseases. However, the suggestion that PrP, normally associated with prion diseases, binds to BACE-1 and reduces its activity has led to the suggestion that the study of this interaction could be of considerable importance to Alzheimer's disease. We therefore undertook to investigate the possible interaction of these two proteins physically and at the level of transcription, translation and APP cleavage. Our findings suggest that mature PrP and BACE-1 do not physically interact, but that altered PrP expression results in altered BACE-1 protein expression and promoter activity. Additionally, overexpression of PrP results in increased cleavage of APP in contrast to previous datas suggesting a reduction. Our findings suggest that any relation between PrP and BACE-1 is indirect. Altered expression of PrP causes changes in the expression of many other proteins which may be as a result of altered copper metabolism.

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