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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 314(5796): 130-133



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.

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Accession: 012897405

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PMID: 17023659

DOI: 10.1126/science.1134108


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