Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branchingReport as inadecuate




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Molecular Brain

, 2:30

First Online: 25 September 2009Received: 11 September 2009Accepted: 25 September 2009

Abstract

BackgroundTDP-43 is an evolutionarily conserved RNA-binding protein implicated in the pathogenesis of frontotemporal dementia FTD, sporadic and familial amyotrophic lateral sclerosis ALS, and possibly other neurodegenerative diseases. In diseased neurons, TDP-43 is depleted in the nucleus, suggesting a loss-of-function pathogenic mechanism. However, the normal function of TDP-43 in postmitotic neurons is largely unknown.

ResultsHere we demonstrate that overexpression of Drosophila TDP-43 dTDP-43 in vivo significantly increases dendritic branching of sensory neurons in Drosophila larvae. Loss of dTDP-43 function, either in a genetic null mutant or through RNAi knockdown, decreased dendritic branching. Further genetic analysis demonstrated a cell-autonomous role for dTDP-43 in dendrite formation. Moreover, human TDP-43 hTDP-43 promoted dendritic branching in Drosophila neurons, and this function was attenuated by mutations associated with ALS.

ConclusionThese findings reveal an essential role for TDP-43 in dendritic structural integrity, supporting the notion that loss of normal TDP-43 function in diseased neurons may compromise neuronal connectivity before neuronal cell loss in FTD and ALS.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-6606-2-30 contains supplementary material, which is available to authorized users.

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Author: Yubing Lu - Jacob Ferris - Fen-Biao Gao

Source: https://link.springer.com/



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