Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis

Anthony Giampetruzzi, Eric W. Danielson, Valentina Gumina, Maryangel Jeon, Sivakumar Boopathy, Robert H. Brown, Antonia Ratti, John E. Landers and Claudia Fallini ()
Additional contact information
Anthony Giampetruzzi: University of Massachusetts Medical School
Eric W. Danielson: University of Massachusetts Medical School
Valentina Gumina: Istituto Auxologico Italiano, IRCCS, Department of Neurology – Stroke Unit and Laboratory of Neuroscience
Maryangel Jeon: University of Massachusetts Medical School
Sivakumar Boopathy: University of Massachusetts Medical School
Robert H. Brown: University of Massachusetts Medical School
Antonia Ratti: Istituto Auxologico Italiano, IRCCS, Department of Neurology – Stroke Unit and Laboratory of Neuroscience
John E. Landers: University of Massachusetts Medical School
Claudia Fallini: University of Massachusetts Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS and other neurodegenerative diseases, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here we show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity, nuclear import, and downstream pathways such as mRNA post-transcriptional regulation. Importantly, we demonstrate that modulation of actin homeostasis can rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion, the most common mutation in ALS patients. Collectively, our data link NCT defects to ALS-associated cellular pathology and propose the regulation of actin homeostasis as a novel therapeutic strategy for ALS and other neurodegenerative diseases.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11837-y 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:10:y:2019:i:1:d:10.1038_s41467-019-11837-y

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

DOI: 10.1038/s41467-019-11837-y

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 ().