RESEARCH HIGHLIGHTS

Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis

Researchers at Nagoya University and Aichi Medical University found that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS). Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology. Moreover, TDP-DiLuc, a novel reporter assay to evaluate TDP-43 dimerization/multimerization, could detect decreased N-terminal dimerization of TDP-43 prior to the TDP-43 pathological changes. Our findings may be important in future research on early pathogenic events related to TDP-43 and in the search for early diagnostic markers or therapeutic strategies for ALS.
This work was published in the journal Science Advances on August 4, 2023.

Key Points
• TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS).
• Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology.
• TDP-DiLuc, a novel reporter assay to evaluate TDP-43 dimerization/multimerization, could detect decreased N-terminal dimerization of TDP-43 prior to the TDP-43 pathological changes.
• Our findings may be important in future research on early pathogenic events related to TDP-43 and in the search for early diagnostic markers or therapeutic strategies for ALS.

Publication

Journal Science Advances
Title Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology
in amyotrophic lateral sclerosis
Authors Kotaro Oiwa, Seiji Watanabe, Kazunari Onodera, Yohei Iguchi, Yukako Kinoshita, Okiru Komine, Akira Sobue, Yohei Okada, Masahisa Katsuno, Koji Yamanaka
DOI 10.1126/sciadv.adf6895

 

Japanese ver.
https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Sci_230805.pdf