HDAC6 Interacts With Poly (GA) and Modulates its Accumulation in c9FTD/ALS

Giulia del Rosso, Yari Carlomagno, Tiffany W. Todd, Caroline Y. Jones, Mercedes Prudencio, Lillian M. Daughrity, Mei Yue, Karen Jansen-West, Jimei Tong, Wei Shao, Yanwei Wu, Monica Castanedes-Casey, Lilia Tabassian, Björn Oskarsson, Karen Ling, Frank Rigo, Dennis W. Dickson, Tso Pang Yao, Leonard Petrucelli, Casey N. CookYong Jie Zhang

Research output: Contribution to journalArticlepeer-review


The aberrant translation of a repeat expansion in chromosome 9 open reading frame 72 (C9orf72), the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), results in the accumulation of toxic dipeptide repeat (DPR) proteins in the central nervous system We have found that, among the sense DPR proteins, HDAC6 specifically interacts with the poly (GA) and co-localizes with inclusions in both patient tissue and a mouse model of this disease (c9FTD/ALS). Overexpression of HDAC6 increased poly (GA) levels in cultured cells independently of HDAC6 deacetylase activity, suggesting that HDAC6 can modulate poly (GA) pathology through a mechanism that depends upon their physical interaction. Moreover, decreasing HDAC6 expression by stereotaxic injection of antisense oligonucleotides significantly reduced the number of poly (GA) inclusions in c9FTD/ALS mice. These findings suggest that pharmacologically reducing HDAC6 levels could be of therapeutic value in c9FTD/ALS.

Original languageEnglish (US)
Article number809942
JournalFrontiers in Cell and Developmental Biology
StatePublished - Jan 12 2022


  • C9orf72
  • HDAC6
  • amyotrophic lateral sclerosis
  • dipeptide repeat proteins
  • frontotemporal dementia

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


Dive into the research topics of 'HDAC6 Interacts With Poly (GA) and Modulates its Accumulation in c9FTD/ALS'. Together they form a unique fingerprint.

Cite this