Open Close
Reference
Citation
Reinecke, J.B., Devos, S.L., McGrath, J.P., Shepard, A.M., Goncharoff, D.K., Tait, D.N., Fleming, S.R., Vincent, M.P., Steinhilb, M.L. (2011). Implicating calpain in tau-mediated toxicity in vivo.  PLoS ONE 6(8): e23865.
FlyBase ID
FBrf0214684
Publication Type
Research paper
Abstract

Alzheimer's disease and other related neurodegenerative disorders known as tauopathies are characterized by the accumulation of abnormally phosphorylated and aggregated forms of the microtubule-associated protein tau. Several laboratories have identified a 17 kD proteolytic fragment of tau in degenerating neurons and in numerous cell culture models that is generated by calpain cleavage and speculated to contribute to tau toxicity. In the current study, we employed a Drosophila tauopathy model to investigate the importance of calpain-mediated tau proteolysis in contributing to tau neurotoxicity in an animal model of human neurodegenerative disease. We found that mutations that disrupted endogenous calpainA or calpainB activity in transgenic flies suppressed tau toxicity. Expression of a calpain-resistant form of tau in Drosophila revealed that mutating the putative calpain cleavage sites that produce the 17 kD fragment was sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant toxicity in the fly retina associated with expression of only the 17 kD tau fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as an important pathway mediating tau neurotoxicity in vivo.

PubMed ID
PubMed Central ID
PMC3157467 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS ONE
    Title
    PLoS ONE
    Publication Year
    2006-
    ISBN/ISSN
    1932-6203
    Data From Reference
    Aberrations (2)
    Alleles (9)
    Genes (4)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (1)
    Transgenic Constructs (7)