Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD.

Authors

Thomas Westergard, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson UniversityFollow
Brigid K Jensen, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University
Xinmei Wen, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson UniversityFollow
Jingli Cai, Farber Institute for Neurosciences, Thomas Jefferson UniversityFollow
Elizabeth Kropf, Stem Cell Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University
Lorraine Iacovitti, Farber Institute for Neurosciences, Department of Neurology, Thomas Jefferson University Medical CollegeFollow
Piera Pasinelli, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson UniversityFollow
Davide Trotti, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

10-11-2016

Comments

This article has been peer reviewed. It was published in: Cell Reports.
Volume 17, Issue 3, 11 October 2016, Pages 645-652.
The published version is available at DOI: 10.1016/j.celrep.2016.09.032
Copyright © 2016 The Authors

Abstract

Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases. While DPR toxic mechanisms continue to be investigated, the potential for DPRs to spread has yet to be determined. Using different experimental cell culture platforms, including spinal motor neurons derived from induced pluripotent stem cells from C9orf72-ALS patients, we found evidence for cell-to-cell spreading of DPRs via exosome-dependent and exosome-independent pathways, which may be relevant to disease.

Recommended Citation

Westergard, Thomas; Jensen, Brigid K; Wen, Xinmei; Cai, Jingli; Kropf, Elizabeth; Iacovitti, Lorraine; Pasinelli, Piera; and Trotti, Davide, "Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD." (2016). Farber Institute for Neuroscience Faculty Papers. Paper 27.
https://jdc.jefferson.edu/farberneursofp/27

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

27732842