title: Reduced expression of BTBD10, an Akt activator, leads to motor neuron death.
abstract: BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A-mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10 suppresses motor neuron death that is induced by a familial amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro. In this study, we further investigated the BTBD10-mediated suppression of motor neuron death. We found that the small interfering RNA-mediated inhibition of BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of neurons, including both motor and touch-receptor neurons, but also a locomotion defect. In addition, we found that the expression of BTBD10 was generally decreased in the motor neurons from patients of sporadic ALS and transgenic mice overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo.
authors.affiliation: Department of Pharmacology, Tokyo Medical University, Shinjuku-ku, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nawa
authors.forename: E
authors.initials: E
authors.lastname: Kage-Nakadai
authors.forename: S
authors.initials: S
authors.lastname: Aiso
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Mitani
authors.forename: M
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D016923:Cell Death / Q000502:physiology; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*
chemical_list: C494432:BTBD10 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt