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Karsten, S.L., Sang, T.K., Gehman, L.T., Chatterjee, S., Liu, J., Lawless, G.M., Sengupta, S., Berry, R.W., Pomakian, J., Oh, H.S., Schulz, C., Hui, K.S., Wiedau-Pazos, M., Vinters, H.V., Binder, L.I., Geschwind, D.H., Jackson, G.R. (2006). A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration.  Neuron 51(5): 549--560.
FlyBase ID
FBrf0193591
Publication Type
Research paper
Abstract

Neurofibrillary tangles (NFT) containing tau are a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD). NFT burden correlates with cognitive decline and neurodegeneration in AD. However, little is known about mechanisms that protect against tau-induced neurodegeneration. We used a cross species functional genomic approach to analyze gene expression in multiple brain regions in mouse, in parallel with validation in Drosophila, to identify tau modifiers, including the highly conserved protein puromycin-sensitive aminopeptidase (PSA/Npepps). PSA protected against tau-induced neurodegeneration in vivo, whereas PSA loss of function exacerbated neurodegeneration. We further show that human PSA directly proteolyzes tau in vitro. These data highlight the utility of using both evolutionarily distant species for genetic screening and functional assessment to identify modifiers of neurodegeneration. Further investigation is warranted in defining the role of PSA and other genes identified here as potential therapeutic targets in tauopathy.

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    Language of Publication
    English
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    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
    Data From Reference
    Alleles (10)
    Genes (9)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (7)