The double-edged sword effect of HDAC6 in Aβ toxicities

Kuan Chung Cheng, Yu Luen Hwang, Hsueh Cheng Chiang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Alzheimer's disease (AD) is marked by cognitive impairment, massive cell death, and reduced life expectancy. Pathologically, accumulated beta-amyloid (Aβ) aggregates and hyperphosphorylated tau protein is the hallmark of the disease. Although changes in cellular function and protein accumulates have been demonstrated in many different AD animal models, the molecular mechanism involved in different cellular functions and the correlation and causative relation between different protein accumulations remain elusive. Our in vivo genetic studies revealed that the molecular mechanisms involved in memory loss and lifespan shortening are different and that tau plays an essential role in mediating Aβ-induced early death. We found that when the first deacetylase (DAC) domain of histone deacetylase 6 (HDAC6) activity was increased, it regulated cortactin deacetylation to reverse Aβ-induced learning and memory deficit, but with no effect on the lifespan of the Aβ flies. On the other hand, an increased amount of the second DAC domain of HDAC6 promoted tau phosphorylation to facilitate Aβ-induced lifespan shortening without affecting learning performance in the Aβ flies. Our data also confirmed decreased acetylation in two major HDAC6 downstream proteins, suggesting increased HDAC6 activity in Aβ flies. Our data established the double-edged sword effect of HDAC6 activity in Aβ-induced pathologies. Not only did we segregate memory loss and lifespan shortening in Aβ flies, but we also provided evidence to link the Aβ with tau signaling.

Original languageEnglish
Article numbere22072
JournalFASEB Journal
Volume36
Issue number1
DOIs
Publication statusPublished - 2022 Jan

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'The double-edged sword effect of HDAC6 in Aβ toxicities'. Together they form a unique fingerprint.

Cite this