An age-related reduction of brain TBPH/TDP-43 levels precedes the onset of locomotion defects in a Drosophila ALS model

• Published in: Neuroscience Vol. 311; pp. 415 - 421
• Main Authors: Cragnaz, L, Klima, R, De Conti, L, Romano, G, Feiguin, F, Buratti, E, Baralle, M, Baralle, F.E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 17-12-2015
• Subjects: aggregation; Aging - metabolism; ALS; Amyotrophic Lateral Sclerosis - physiopathology; Animals; Animals, Genetically Modified; Brain - metabolism; Disease Models, Animal; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila melanogaster; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Locomotion - physiology; Mice; Neurology; RNA Interference; RNA, Messenger - metabolism; Species Specificity; TDP-43/TBPH levels; TBPH; TAR DNA-binding protein-43; Drosophila; ALS; CNS; aggregation; 12xQ/N; repeated TDP-43 amino acid sequence 331–369; amyotrophic lateral sclerosis; central nervous system; TDP-43/TBPH levels; TDP-43; TAR DNA-binding protein-43 Drosophila melanogaster ortholog
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2015.10.037

Highlights • TDP-43 levels decrease physiologically during aging in Drosophila and mice. • The reduction is seen at protein and mRNA level in the brain. • Aggregation does not hamper normal development and early adult life. • TBPH reduction combined with the presence of aggregates triggers a locomotive defect. • A similar pathway may be active in the pathogenesis of human ALS.