Chemogenomic analysis reveals key role for lysine acetylation in regulating Arc stability

Jasmin Lalonde (), Surya A. Reis, Sudhir Sivakumaran, Carl S. Holland, Hendrik Wesseling, John F. Sauld, Begum Alural, Wen-Ning Zhao, Judith A. Steen and Stephen J. Haggarty ()
Additional contact information
Jasmin Lalonde: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School
Surya A. Reis: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School
Sudhir Sivakumaran: Boston University School of Medicine
Carl S. Holland: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School
Hendrik Wesseling: F.M. Kirby Center for Neurobiology, Harvard Medical School
John F. Sauld: F.M. Kirby Center for Neurobiology, Harvard Medical School
Begum Alural: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School
Wen-Ning Zhao: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School
Judith A. Steen: F.M. Kirby Center for Neurobiology, Harvard Medical School
Stephen J. Haggarty: Massachusetts General Hospital, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract The role of Arc in synaptic plasticity and memory consolidation has been investigated for many years with recent evidence that defects in the expression or activity of this immediate-early gene may also contribute to the pathophysiology of brain disorders including schizophrenia and fragile X syndrome. These results bring forward the concept that reversing Arc abnormalities could provide an avenue to improve cognitive or neurological impairments in different disease contexts, but how to achieve this therapeutic objective has remained elusive. Here, we present results from a chemogenomic screen that probed a mechanistically diverse library of small molecules for modulators of BDNF-induced Arc expression in primary cortical neurons. This effort identified compounds with a range of influences on Arc, including promoting its acetylation—a previously uncharacterized post-translational modification of this protein. Together, our data provide insights into the control of Arc that could be targeted to harness neuroplasticity for clinical applications.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01750-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01750-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01750-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().