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Isoform Specific Amyloid-β Protein Precursor Metabolism

Isoform Specific Amyloid-β Protein Precursor Metabolism Alzheimer's amyloid-β protein precursor (AβPP) can occur in different isoforms, among them AβPP _{751} , which is the most abundant isoform in non-neuronal tissues, and AβPP _{695} , often referred to as the neuronal isoform. However, few isoform-specific roles have been addressed. In the work here described, AβPP isoforms, both endogenous and as cDNA fusions with green fluorescent protein (GFP), were used to permit isoform-specific monitoring in terms of intracellular processing and targeting. Differences were particularly marked in the turnover rates of the immature isoforms, with AβPP _{751} having a faster turnover rate than AβPP _{695} (0.8 h and 1.2 h respectively for endogenous proteins and 1.1 h and 2.3 h for transfected proteins). Hence, AβPP _{751} matures faster. Additionally, AβPP _{751} responded to both okadaic acid (OA) and phorbol 12-myristate 13-acetate (PMA), as determined by sAβPP production, with PMA inducing a more robust response. For the AβPP _{695} isoform, however, although PMA produced a strong response, OA failed to elicit such an induction in sAβPP production, implicating isoform specificity in phosphorylation regulated events. In conclusion, it seems that the AβPP _{695} isoform is processed/metabolized at a slower rate and responds differently to OA when compared to the AβPP _{751} isoform. The relevance of isoform-specific processing in relation to Alzheimer's disease needs to be further investigated, given the predominance of the AβPP _{695} isoform in neuronal tissues and isoform-specific alterations in expression levels associated with the pathology. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Alzheimer's Disease IOS Press

Isoform Specific Amyloid-β Protein Precursor Metabolism

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Publisher
IOS Press
Copyright
Copyright © 2007 by IOS Press, Inc
ISSN
1387-2877
eISSN
1875-8908
Publisher site
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Abstract

Alzheimer's amyloid-β protein precursor (AβPP) can occur in different isoforms, among them AβPP _{751} , which is the most abundant isoform in non-neuronal tissues, and AβPP _{695} , often referred to as the neuronal isoform. However, few isoform-specific roles have been addressed. In the work here described, AβPP isoforms, both endogenous and as cDNA fusions with green fluorescent protein (GFP), were used to permit isoform-specific monitoring in terms of intracellular processing and targeting. Differences were particularly marked in the turnover rates of the immature isoforms, with AβPP _{751} having a faster turnover rate than AβPP _{695} (0.8 h and 1.2 h respectively for endogenous proteins and 1.1 h and 2.3 h for transfected proteins). Hence, AβPP _{751} matures faster. Additionally, AβPP _{751} responded to both okadaic acid (OA) and phorbol 12-myristate 13-acetate (PMA), as determined by sAβPP production, with PMA inducing a more robust response. For the AβPP _{695} isoform, however, although PMA produced a strong response, OA failed to elicit such an induction in sAβPP production, implicating isoform specificity in phosphorylation regulated events. In conclusion, it seems that the AβPP _{695} isoform is processed/metabolized at a slower rate and responds differently to OA when compared to the AβPP _{751} isoform. The relevance of isoform-specific processing in relation to Alzheimer's disease needs to be further investigated, given the predominance of the AβPP _{695} isoform in neuronal tissues and isoform-specific alterations in expression levels associated with the pathology.

Journal

Journal of Alzheimer's Disease – IOS Press

Published: Jan 1, 2007

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