Rinsho Shinkeigaku (Clinical Neurology)

Symposium 33

Aberration of the spliceosome in amyotrophic lateral sclerosis

Tomohiko Ishihara, M.D., Ph.D.1)2), Akiyoshi Kakita, M.D., Ph.D.3), Hitoshi Takahashi, M.D., Ph.D.4), Osamu Onodera, M.D., Ph.D.2) and Masatoyo Nishizawa, M.D., Ph.D.1)

1)Department of Neurology, Brain Research Institute, Niigata University
2)Department of Molecular Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, Niigata University
3)Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, Niigata University
4)Department of Pathology, Bioresource-based Researches, Brain Research Institute, Niigata University

TDP-43 is a nuclear protein that plays a role in RNA metabolism, and its dysfunction has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a typical adult-onset motor neuron disease. We investigated RNA metabolism in relation to TDP-43 function in neuronal tissues affected by ALS, and found a decrease in the number of nuclear GEM bodies, as well as reduced expression of minor spliceosomes, which are functional RNA-protein complexes. Similar features have been reported in spinal muscular atrophy (SMA), a motor neuron disease affecting infants. These findings, together with those reported in SMA, strongly suggest that reduction of minor spliceosomes has an important role in the pathomechanism underlying the selective degeneration of motor neurons characteristic of both ALS and SMA.
Full Text of this Article in Japanese PDF (282K)

(CLINICA NEUROL, 54: 1155－1157, 2014)
key words: amyotrophic lateral sclerosis, spinal muscular atrophy, GEM body, minor spliceosome

(Received: 24-May-14)