Reduced expression of BTBD10, an Akt activator, leads to motor neuron death
| Autor: | Masaaki Matsuoka, Koichi Okamoto, Mikiro Nawa, Sadakazu Aiso, Eriko Kage-Nakadai, Shohei Mitani |
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| Rok vydání: | 2012 |
| Předmět: |
Genetically modified mouse
animal diseases Phosphatase SOD1 Mice Transgenic Biology Mice medicine Animals Humans Gene Silencing Amyotrophic lateral sclerosis Caenorhabditis elegans Molecular Biology Protein kinase B Motor Neurons Genetics Original Paper Cell Death Activator (genetics) Intracellular Signaling Peptides and Proteins Nuclear Proteins nutritional and metabolic diseases Cell Biology Motor neuron biology.organism_classification medicine.disease nervous system diseases Cell biology HEK293 Cells medicine.anatomical_structure nervous system Proto-Oncogene Proteins c-akt HeLa Cells |
| Zdroj: | Cell Death & Differentiation. 19:1398-1407 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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