The TAR DNA-binding protein Mr 43 kDa(TDP-43)is a major component of the taunegative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS)and frontotemporal lobar degeneration, which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer’s disease, forming a group of TDP-43 proteinopathies. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role in the pathological process. Understanding the mechanism of phosphorylation and truncation of TDP-43, and aggregate formation, may be crucial to clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapies.
A New Dementia Group Caused by TDP-43 Abnormality
1 Department of Pcychiatry, Graduate School of Comprehensive Human Sciences, University of Tsukuba
2 Department of Neuropathology and Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba
3 Dementia Research Project, Tokyo Metropolitan Institute of Medical Science
2 Department of Neuropathology and Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba
3 Dementia Research Project, Tokyo Metropolitan Institute of Medical Science
Psychiatria et Neurologia Japonica
113: 574-583, 2011