Premium
Tau – an inhibitor of deacetylase HDAC6 function
Author(s) -
Perez Mar,
SantaMaria Ismael,
De Barreda Elena Gomez,
Zhu Xiongwei,
Cuadros Raquel,
Cabrero Jose Roman,
SanchezMadrid Francisco,
Dawson Ha.,
Vitek Michael P.,
Perry George,
Smith Mark A.,
Avila Jesus
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06102.x
Subject(s) - hdac6 , acetylation , tubulin , microtubule , tau protein , histone deacetylase , hdac4 , chemistry , microtubule associated protein , histone deacetylase inhibitor , hdac10 , autophagy , protein subunit , biology , biochemistry , sap30 , histone , microbiology and biotechnology , alzheimer's disease , disease , medicine , apoptosis , histone methyltransferase , histone h2a , gene
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.