%0 Journal Article
%T Drosophila Answers to TDP-43 Proteinopathies
%A Maurizio Romano
%A Fabian Feiguin
%A Emanuele Buratti
%J Journal of Amino Acids
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/356081
%X Initially implicated in the pathogenesis of CFTR and HIV-1 transcription, nuclear factor TDP-43 was subsequently found to be involved in the origin and development of several neurodegenerative diseases. In 2006, in fact, it was reported for the first time the cytoplasmic accumulation of TDP-43 in ubiquitin-positive inclusions of ALS and FTLD patients, suggesting the presence of a shared underlying mechanism for these diseases. Today, different animal models of TDP-43 proteinopathies are available in rodents, nematodes, fishes, and flies. Although these models recapitulate several of the pathological features found in patients, the mechanisms underpinning the progressive neuronal loss observed in TDP-43 proteinopathies remain to be characterized. Compared to other models, Drosophila are appealing because they combine the presence of a sophisticated brain with the possibility to investigate quickly and massively phenotypic genetic modifiers as well as possible therapeutic strategies. At present, the development of TDP-43-related Drosophila models has further strengthened the hypothesis that both TDP-43 ˇ°loss-of-functionˇ± and ˇ°gain-of-functionˇ± mechanisms can contribute to disease. The aim of this paper is to describe and compare the results obtained in a series of transgenic and knockout flies, along with the information they have generated, towards a better understanding of the mechanisms underlying TDP-43 proteinopathies. 1. Introduction Nowadays, Drosophila is one of the most widely used model organism for studying complex genetic and biological problems. Drosophila was introduced as an experimental model in the early twentieth century. Although there are several different Drosophila species which differ in habitat, morphology, and genetic background, D. melanogaster is the species with the highest degree of homology with humans. Over the years, many mutants of Drosophila melanogaster have been isolated and many transgenic strains have been created as model systems for the study of human disease [1], leading to the observation that more than 70% of human loci correlated with pathological conditions have orthologs in Drosophila melanogaster [2]. Compared to other animal models used to study the mechanisms underlying many disease onset/progression, Drosophila present several advantages: the life span is short (from 40 to 120 days) [3]; the genome is compact, with only 4 pairs of homologous chromosomes and roughly 13600 genes [4]. The importance of Drosophila melanogaster is further supported by the fact that it represents an animal model where the
%U http://www.hindawi.com/journals/jaa/2012/356081/