Calcineurin overexpression regulates APP metabolism - Advances in Alzheimer's Disease

AAD > Vol.2 No.3, September 2013

Calcineurin overexpression regulates APP metabolism ()

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DOI: 10.4236/aad.2013.23014 5,612 Downloads 8,495 Views Citations

Author(s)

Suruchi Utreja, Sean J. Miller, Aleister Saunders

Affiliation(s)

.
Department of Biology, Drexel University, Philadelphia, USA.

ABSTRACT

Alzheimer’s disease (AD) is a complex neurodegenerative disease, pathologically characterized by the accumulation of β-amyloid peptide (Aβ) and intraneuronal neurofibrillary tangles. Production of the Aβpeptide by the regulated intra-membrane proteolysis of the β-amyloid precursor protein (APP) is a central event in AD.Cognitive decline observed in AD models is dependent on Aβgeneration. One of the downstream effects mediated by soluble Aβoligomersincludes the hyperactivation of calcineurin (CaN), a Ca2+and calmodulin (CaM)-dependent, serinethreonine protein phosphatase. CaN is one of the major phosphatase associated with cognitive and neurodegenerative effects of Aβ. A specific isoform of CaN, CaNAβ, is one of the most up-regulated mRNAs in brains of early stage AD patients. While Aβ’s ability to activate CaN has been well studied, not much is known about how increased levels of CaN in AD brain can contribute towards Aβgeneration. In this study we specifically investigate if increased levels of CaNAβ regulate APP metabolism. Our results demonstrate that increased CaNAβ expressionleads to increased APP levels and increased proteolytic products of APP, including Aβ. The data suggest that upregulation of CaN levels could contribute to neurodegeneration observed in AD by increasing levels ofAβ, potentially forming a pathogenic feed forward loop.

KEYWORDS

Alzheimer’s Disease; Calcineurin; APP; Aβ; FK506

Share and Cite:

Utreja, S. , J. Miller, S. and Saunders, A. (2013) Calcineurin overexpression regulates APP metabolism. Advances in Alzheimer's Disease, 2, 109-116. doi: 10.4236/aad.2013.23014.

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