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Hiroshi Tsuji, Tetsuaki Arai, Fuyuki Kametani, Takashi Nonaka, Makiko Yamashita, Masami Suzukake, Masato Hosokawa, Mari Yoshida, Hiroyuki Hatsuta, Masaki Takao, Yuko Saito, Shigeo Murayama, Haruhiko Akiyama, Masato Hasegawa, David M. A. Mann, Akira Tamaoka, Molecular analysis and biochemical classification of TDP-43 proteinopathy, Brain, Volume 135, Issue 11, November 2012, Pages 3380–3391, https://doi.org/10.1093/brain/aws230
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Abstract
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kDa pathology are progressive neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated TAR DNA-binding protein of 43 kDa. These TAR DNA-binding protein 43 proteinopathies can be classified into subtypes, which are closely correlated with clinicopathological phenotypes, although the differences in the molecular species of TAR DNA-binding protein 43 in these diseases and the biological significance thereof, remain to be clarified. Here, we have shown that although the banding patterns of abnormally phosphorylated C-terminal fragments of TAR DNA-binding protein 43 differ between the neuropathological subtypes, these are indistinguishable between multiple brain regions and spinal cord in individual patients. Immunoblot analysis of protease-resistant TAR DNA-binding protein 43 demonstrated that the fragment patterns represent different conformations of TAR DNA-binding protein 43 molecular species in the diseases. These results suggest a new clinicopathological classification of TAR DNA-binding protein 43 proteinopathies based on their molecular properties.
