Pan-HDAC Inhibitors Promote Tau Aggregation by Increasing the Level of Acetylated Tau.

Abstract

Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer's disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.

• Authors: Hyeanjeong Jeong, Seulgi Shin, Jun-Seok Lee, Soo Hyun Lee, Ja-Hyun Baik, Sungsu Lim, Yun Kyung Kim
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 17 (Sep 01 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31480543 (Publication Type: Journal Article)

Chemical References

• Histone Deacetylase Inhibitors
• tau Proteins
• Histone Deacetylases

Topics

• Acetylation
• Alzheimer Disease (enzymology, metabolism)
• HEK293 Cells
• Histone Deacetylase Inhibitors (pharmacology)
• Histone Deacetylases (metabolism)
• Humans
• Protein Aggregation, Pathological
• Protein Processing, Post-Translational
• tau Proteins (metabolism)