Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
TLDR
The cellular processes involved in the pathogeneses of ALS and FTLD, such as post-translational modifications, RNA metabolism, liquid–liquid phase separation, proteolysis, and the potential prion-like propagation propensity of the TDP-43 inclusions are described.Abstract:
TAR DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in pivotal cellular functions, especially in RNA metabolism. Hyperphosphorylated and ubiquitinated TDP-43-positive neuronal cytoplasmic inclusions are identified in the brain and spinal cord in most cases of amyotrophic lateral sclerosis (ALS) and a substantial proportion of frontotemporal lobar degeneration (FTLD) cases. TDP-43 dysfunctions and cytoplasmic aggregation seem to be the central pathogenicity in ALS and FTLD. Therefore, unraveling both the physiological and pathological mechanisms of TDP-43 may enable the exploration of novel therapeutic strategies. This review highlights the current understanding of TDP-43 biology and pathology, describing the cellular processes involved in the pathogeneses of ALS and FTLD, such as post-translational modifications, RNA metabolism, liquid–liquid phase separation, proteolysis, and the potential prion-like propagation propensity of the TDP-43 inclusions.read more
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References
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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
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Peter Walter,David Ron +1 more
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TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Tetsuaki Arai,Masato Hasegawa,Haruhiko Akiyama,Kenji Ikeda,Takashi Nonaka,Hiroshi Mori,David M. A. Mann,Kuniaki Tsuchiya,Mari Yoshida,Yoshio Hashizume,Tatsuro Oda +10 more
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