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  • Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Science (New York, N.Y.) (2006-10-07)
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
PMID17023659
ABSTRACT

Ubiquitin-positive, tau- and alpha-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.