Tau--an inhibitor of deacetylase HDAC6 function.

Journal Article

Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.

Full Text

Duke Authors

Cited Authors

  • Perez, M; Santa-Maria, I; Gomez de Barreda, E; Zhu, X; Cuadros, R; Cabrero, JR; Sanchez-Madrid, F; Dawson, HN; Vitek, MP; Perry, G; Smith, MA; Avila, J

Published Date

  • June 2009

Published In

Volume / Issue

  • 109 / 6

Start / End Page

  • 1756 - 1766

PubMed ID

  • 19457097

Electronic International Standard Serial Number (EISSN)

  • 1471-4159

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2009.06102.x

Language

  • eng

Conference Location

  • England