Alzheimer's disease β-secretase BACE1 is not a neuron-specific enzyme

Steffen Roßner, Christine Lange-Dohna, Ulrike Zeitschel, J. Regino Perez-Polo

    Research output: Contribution to journalReview articlepeer-review

    104 Scopus citations

    Abstract

    The brains of Alzheimer's disease (AD) patients are morphologically characterized by neurofibrillar abnormalities and by parenchymal and cerebrovascular deposits of β-amyloid peptides. The generation of β-amyloid peptides by proteolytical processing of the amyloid precursor protein (APP) requires the enzymatic activity of the β-site APP cleaving enzyme 1 (BACE1). The expression of this enzyme has been localized to the brain, in particular to neurons, indicating that neurons are the major source of β-amyloid peptides in brain. Astrocytes, on the contrary, are known to be important for β-amyloid clearance and degradation, for providing trophic support to neurons, and for forming a protective barrier between β-amyloid deposits and neurons. However, under certain conditions related to chronic stress, the role of astrocytes may not be beneficial. Here we present evidence demonstrating that astrocytes are an alternative source of BACE1 and therefore may contribute to ß-amyloid plaque formation. While resting astroyctes in brain do not express BACE1 at detectable levels, cultured astrocytes display BACE1 promoter activity and express BACE1 mRNA and enzymatically active BACE1 protein. Additionally, in animal models of chronic gliosis and in brains of AD patients, there is BACE1 expression in reactive astrocytes. This would suggest that the mechanism for astrocyte activation plays a role in the development of AD and that therapeutic strategies that target astrocyte activation in brain may be beneficial for the treatment of AD. Also, there are differences in responses to chronic versus acute stress, suggesting that one consequence of chronic stress is an incremental shift to different phenotypic cellular states.

    Original languageEnglish (US)
    Pages (from-to)226-234
    Number of pages9
    JournalJournal of neurochemistry
    Volume92
    Issue number2
    DOIs
    StatePublished - Jan 1 2005

    Keywords

    • β-amyloid peptides
    • Aging
    • Alzheimer's disease
    • Gliosis
    • NF-κB
    • Stress response

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Fingerprint Dive into the research topics of 'Alzheimer's disease β-secretase BACE1 is not a neuron-specific enzyme'. Together they form a unique fingerprint.

    Cite this