Dementia Japan 25: 129-136, 2011

Molecular pathomechanisms of TDP-43 proteinopathies revealed by Drosophila models

Yoshitaka Nagai, Nobuhiro Fujikake

Department of Degenerative Neurological Diseases, National Institute of Neuroscience,National Center of Neurology and Psychiatry

    TDP-43 proteinopathies are a group of neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), which are characterized by aggregation and accumulation of TDP-43 in inclusions associated with a decrease in its normal nuclear localization in affected neurons.Genetic analyses have identified various mutations in the TDP-43 gene responsible for many FALS families and some FTLD families, suggesting that abnormalities of TDP-43 could be primary events in the pathogenesis.Toward establishing aminal models of TDP-43 proteinopathies and understanding their pathogenesis, many researchers now employ Drosophila melanogaster to model the disease because of its short life-span and advantages for genetic analyses.We here review recent advances in the pathogenesis of TDP-43 proteinopathies, especially those which have been revealed by the use of Drosophila models of TDP-43 proteinopathies.

Address correspondence to Dr. Yoshitaka Nagai,Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry (4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan)