Mar Pérez1,2,3, Ismael Santa‐María4,1,3, Elena Gómez de Barreda1, Xiongwei Zhu5, Raquel Cuadros1, J. Román Cabrero6,7, Francisco Sánchez‐Madrid6,7, Hana N. Dawson8, Michael P. Vitek8, George Perry9,5, Mark A. Smith5, Jesús Ávila4,1
1Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
2Facultad de Medicina, Universidad Autonoma de Madrid (UAM), Madrid, Spain
3These two authors contributed equally to this work.
4CIBERNED, MADRID, Spain
5Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
6Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain;
7Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, 28006 Madrid, Spain
8Division of Neurology, Duke University, Durham, North Carolina, USA
9College of Science, University of Texas at San Antonio, Texas, USA
Tóm tắt
AbstractAnalysis 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.
