Molecular analysis and biochemical classification of TDP-43 proteinopathy

作者：Tsuji Hiroshi; Arai Tetsuaki; Kametani Fuyuki; Nonaka Takashi; Yamashita Makiko; Suzukake Masami; Hosokawa Masato; Yoshida Mari; Hatsuta Hiroyuki; Takao Masaki; Saito Yuko; Murayama Shigeo; Akiyama Haruhiko; Hasegawa Masato^*; Mann David M A; Tamaoka Akira

来源：Brain, 2012, 135(11): 3380-3391.

DOI：10.1093/brain/aws230

• amyotrophic lateral sclerosis
• frontotemporal lobar degeneration
• TDP-43
• classification

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.

• 出版日期2012-11
• 单位河北医科大学