title: A new cellular model of pathological TDP-43: The neurotoxicity of stably expressed CTF25 of TDP-43 depends on the proteasome.
abstract: The C-terminal fragments-25(CTF25) of TDP-43 is a fragment of TAR DNA-binding protein 43kDa (TDP-43), which is involved in RNA metabolism, neurite outgrowth, and neuronal development and stress granules. Not until recently did evidence suggest that CTF25 might play an important role in amyotrophic lateral sclerosis (ALS) pathogenesis. However, mechanical details on CTF25 causing motor neuron degeneration still remain unknown. To study the toxicity of CTF25 of TDP-43, we established a cellular model stably expressing CTF25 of TDP-43. Herein, we found that stably expressed CTF25 could induce significant oxidative stress and was mainly degraded by the proteasome pathway in cells. Furthermore, the neurotoxicity of CTF25 of TDP-43 was dependent on proteasome activity. In addition, electron microscopy showed mitochondrial swelling and cristae dilation in cells expressing CTF25 and that CTF25 aggregates were characterized by filamentous bundles and electron dense granular material. In conclusion, the new cellular model mimics classical toxic TDP-43 cellular model and interestingly the toxicity of CTF25 is dependent on the proteasome.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang, Hebei 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang, Hebei 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang, Hebei 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
authors.forename: P
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang, Hebei 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei 050000, People's Republic of China. Electronic address: hblicy5@aliyun.com.
authors.forename: C
authors.initials: C
authors.lastname: Li
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D046988:Proteasome Endopeptidase Complex
keywords: TDP-43; amyotrophic lateral sclerosis; the CTF25 of TDP-43