Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

Manuela Neumann, Deepak M. Sampathu, Linda K. Kwong, Adam C. Truax, Matthew C. Micsenyi, Thomas T. Chou, Jennifer Bruce, Theresa Schuck, Murray Grossman, Christopher M. Clark, Leo F. McCluskey, Bruce L. Miller, Eliezer Masliah, Ian R. Mackenzie, Howard Feldman, Wolfgang Feiden, Hans A. Kretzschmar, John Q. Trojanowski, Virginia M.-Y. Lee

2006Published

6.1KCitations

0References

journal articleType

Abstract

Ubiquitin-positive, tau- and α-synuclein–negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.

Journal: Science

Publisher: American Association for the Advancement of Science (AAAS)

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