Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching
<p>Abstract</p> <p>Background</p> <p>TDP-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 d...
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| Format: | Article |
| Language: | English |
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BMC
2009-09-01
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| Series: | Molecular Brain |
| Online Access: | http://www.molecularbrain.com/content/2/1/30 |
| _version_ | 1828297097235922944 |
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| author | Lu Yubing Ferris Jacob Gao Fen-Biao |
| author_facet | Lu Yubing Ferris Jacob Gao Fen-Biao |
| author_sort | Lu Yubing |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>TDP-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.</p> <p>Results</p> <p>Here we demonstrate that overexpression of <it>Drosophila </it>TDP-43 (dTDP-43) in vivo significantly increases dendritic branching of sensory neurons in <it>Drosophila </it>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 <it>Drosophila </it>neurons, and this function was attenuated by mutations associated with ALS.</p> <p>Conclusion</p> <p>These 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.</p> |
| first_indexed | 2024-04-13T12:21:38Z |
| format | Article |
| id | doaj.art-84e4495dd3954cce8afdff56f3df4b7d |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-04-13T12:21:38Z |
| publishDate | 2009-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-84e4495dd3954cce8afdff56f3df4b7d2022-12-22T02:47:12ZengBMCMolecular Brain1756-66062009-09-01213010.1186/1756-6606-2-30Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branchingLu YubingFerris JacobGao Fen-Biao<p>Abstract</p> <p>Background</p> <p>TDP-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.</p> <p>Results</p> <p>Here we demonstrate that overexpression of <it>Drosophila </it>TDP-43 (dTDP-43) in vivo significantly increases dendritic branching of sensory neurons in <it>Drosophila </it>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 <it>Drosophila </it>neurons, and this function was attenuated by mutations associated with ALS.</p> <p>Conclusion</p> <p>These 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.</p>http://www.molecularbrain.com/content/2/1/30 |
| spellingShingle | Lu Yubing Ferris Jacob Gao Fen-Biao Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching Molecular Brain |
| title | Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching |
| title_full | Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching |
| title_fullStr | Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching |
| title_full_unstemmed | Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching |
| title_short | Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching |
| title_sort | frontotemporal dementia and amyotrophic lateral sclerosis associated disease protein tdp 43 promotes dendritic branching |
| url | http://www.molecularbrain.com/content/2/1/30 |
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