Rinsho Shinkeigaku (Clinical Neurology)


Molecular mechanism of amyotrophic lateral sclerosis (ALS) from the viewpoint of the formation and degeneration of transactive response DNA-binding protein 43 kDa (TDP-43) inclusions

Sou Kasahara, M.D.1), Tomohiko Ishihara, M.D., Ph.D.1), Yuka Koike, M.D., Ph.D.1), Akihiro Sugai, M.D., Ph.D.1) and Osamu Onodera, M.D., Ph.D.1)

1)Department of Neurology, Brain Research Institute, Niigata University

Sporadic amyotrophic lateral sclerosis (SALS) and many cases of familial ALS (FALS) demonstrate cytoplasmic transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusion bodies. Thus, TDP-43 plays a vital role in ALS pathogenesis. Functional analysis of the ALS causative genes advanced the elucidation of the mechanism associated with the formation and degradation of TDP-43 aggregates. Stress granules, which are non-membranous organelles, are attracting attention as sites of aggregate formation, with involvement of FUS and C9orf72. Concurrently, ALS causative genes related to the ubiquitin-proteasome and autophagy systems, which are aggregate degradation mechanisms, have also been reported. Therefore, therapeutic research based on the molecular pathology common to SALS and FALS has been advanced.
Full Text of this Article in Japanese PDF (618K)

(CLINICA NEUROL, 60: 109|116, 2020)
key words: amyorophic lateral sclerosis, molecular pathogenesis, TDP-43, inclusion body formation, aggregate degradation

(Received: 28-Aug-19)