Advanced search
Publication Cover
Journal of Neurogenetics Volume 29, 2015 - Issue 2-3
Submit an article Journal homepage
567
Views
47
CrossRef citations to date
0
Altmetric
ORIGINAL ARTICLE

Rapamycin alleviates pathogenesis of a new Drosophila model of ALS-TDP

Ching-Wei ChengInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
,
Meng-Jau LinInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan
&
Che-Kun James ShenInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Institute of Molecular Biology, Academia Sinica, Taipei, TaiwanCorrespondence[email protected]
Pages 59-68 | Received 03 Mar 2015, Accepted 27 Jul 2015, Published online: 29 Jul 2015

References

  • Aoki, N., Murray, M.E., Ogaki, K., Fujioka, S., Rutherford, N.J., Rademakers, R., et al. (2015). Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A. Acta Neuropathol, 129, 53–64.
  • Ayala, Y.M., Misteli, T., & Baralle, F.E. (2008). TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proc Natl Acad Sci U S A, 105, 3785–3789.
  • Barmada, S.J., Serio, A., Arjun, A., Bilican, B., Daub, A., Ando, D.M., et al. (2014). Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol, 10, 677–685.
  • Benzer, S. (1967). Behavioral mutants of Drosophila isolated by countercurrent distribution. Proc Natl Acad Sci U S A, 58, 1112–1119.
  • Bose, J.K., Huang, C.C., & Shen, C.K. (2011). Regulation of autophagy by neuropathological protein TDP-43. J Biol Chem, 286, 44441–44448.
  • Bose, J.K., Wang, I.F., Hung, L., Tarn, W.Y., & Shen, C.K. (2008). TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing. J Biol Chem, 283, 28852–28859.
  • Brady, O.A., Meng, P., Zheng, Y., Mao, Y., & Hu, F. (2011). Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. J Neurochem, 116, 248–259.
  • Buratti, E., & Baralle, F.E. (2001). Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J Biol Chem, 276, 36337–36343.
  • Buratti, E., & Baralle, F.E. (2009). The molecular links between TDP-43 dysfunction and neurodegeneration. Adv Genet, 66, 1–34.
  • Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y.M., & Baralle, F.E. (2005). TDP-43 binds heterogeneous nuclear ribo nucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J Biol Chem, 280, 37572–37584.
  • Buratti, E., De Conti, L., Stuani, C., Romano, M., Baralle, M., & Baralle, F. (2010). Nuclear factor TDP-43 can affect selected microRNA levels. FEBS J, 277, 2268–2281.
  • Buratti, E., Dork, T., Zuccato, E., Pagani, F., Romano, M., & Baralle, F.E. (2001). Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J, 20, 1774–1784.
  • Caccamo, A., Majumder, S., Deng, J.J., Bai, Y., Thornton, F.B., & Oddo, S. (2009). Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability. J Biol Chem, 284, 27416–27424.
  • Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010). Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem, 285, 13107–13120.
  • Chen-Plotkin, A.S., Lee, V.M., & Trojanowski, J.Q. (2010). TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol, 6, 211–220.
  • Chiang, P.M., Ling, J., Jeong, Y.H., Price, D.L., Aja, S.M., & Wong, P.C. (2010). Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc Natl Acad Sci U S A, 107, 16320–16324.
  • Crews, L., Spencer, B., Desplats, P., Patrick, C., Paulino, A., Rockenstein, E., et al. (2010). Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PloS One, 5, e9313.
  • Diaper, D.C., Adachi, Y., Sutcliffe, B., Humphrey, D.M., Elliott, C.J., Stepto, A., et al. (2013). Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss-of-function phenotypes. Hum Mol Genet, 22, 1539–1557.
  • Estes, P.S., Boehringer, A., Zwick, R., Tang, J.E., Grigsby, B., & Zarnescu, D.C. (2011). Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS. Hum Mol Genet, 20, 2308–2321.
  • Feiguin, F., Godena, V.K., Romano, G., D’Ambrogio, A., Klima, R., & Baralle, F.E. (2009). Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett, 583, 1586–1592.
  • Fiesel, F.C., Voigt, A., Weber, S.S., Van den Haute, C., Waldenmaier, A., Gorner, K., et al. (2010). Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J, 29, 209–221.
  • Fuentealba, R.A., Udan, M., Bell, S., Wegorzewska, I., Shao, J., Diamond, M.I., et al. (2010). Interaction with polyglutamine aggregates reveals a Q/N-rich domain in TDP-43. J Biol Chem, 285, 26304–26314.
  • Gendron, T.F., Josephs, K.A., & Petrucelli, L. (2010). Review: transactive response DNA-binding protein 43 (TDP-43): mechanisms of neurodegeneration. Neuropathol Appl Neurobiol, 36, 97–112.
  • Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S.R., Jangamreddy, J.R., Mehrpour, M., et al. (2014). Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol, 112, 24–49.
  • Gijselinck, I., Sleegers, K., Engelborghs, S., Robberecht, W., Martin, J.J., Vandenberghe, R., et al. (2009). Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS. Neurobiol Aging, 30, 1329–1331.
  • Grad, L.I., Fernando, S.M., & Cashman, N.R. (2015). From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis. Neurobiol Dis, 77, 257–265.
  • Gregory, J.M., Barros, T.P., Meehan, S., Dobson, C.M., & Luheshi, L.M. (2012). The aggregation and neurotoxicity of TDP-43 and its ALS-associated 25 kDa fragment are differentially affected by molecular chaperones in Drosophila. PloS One, 7, e31899.
  • Guerreiro, R.J., Schymick, J.C., Crews, C., Singleton, A., Hardy, J., & Traynor, B.J. (2008). TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis. PloS One, 3, e2450.
  • Hanson, K.A., Kim, S.H., Wassarman, D.A., & Tibbetts, R.S. (2010). Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS). J Biol Chem, 285, 11068–11072.
  • Harris, H., & Rubinsztein, D.C. (2012). Control of autophagy as a therapy for neurodegenerative disease. Nat Rev Neurol, 8, 108–117.
  • Hazelett, D.J., Chang, J.C., Lakeland, D.L., & Morton, D.B. (2012). Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila. G3 (Bethesda), 2, 789–802.
  • Huang, C., Tong, J., Bi, F., Zhou, H., & Xia, X.G. (2012). Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats. J Clin Invest, 122, 107–118.
  • Huang, C.C., Bose, J.K., Majumder, P., Lee, K.H., Huang, J.T., Huang, J.K., & Shen, C.K. (2014). Metabolism and mis-metabolism of the neuropathological signature protein TDP-43. J Cell Sci, 127, 3024–3038.
  • Igaz, L.M., Kwong, L.K., Lee, E.B., Chen-Plotkin, A., Swanson, E., Unger, T., et al. (2011). Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Invest, 121, 726–738.
  • Iguchi, Y., Katsuno, M., Niwa, J., Takagi, S., Ishigaki, S., Ikenaka, K., et al. (2013). Loss of TDP-43 causes age-dependent progressive motor neuron degeneration. Brain, 136, 1371–1382.
  • Janssens, J., Wils, H., Kleinberger, G., Joris, G., Cuijt, I., Ceuterick-de Groote, C., et al. (2013). Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol Neurobiol, 48, 22–35.
  • Joardar, A., Menzl, J., Podolsky, T.C., Manzo, E., Estes, P.S., Ashford, S., & Zarnescu, D.C. (2015). PPAR gamma activation is neuroprotective in a Drosophila model of ALS based on TDP-43. Hum Mol Genet, 24, 1741–1754.
  • Kim, H.J., Raphael, A.R., LaDow, E.S., McGurk, L., Weber, R.A., Trojanowski, J.Q., et al. (2014). Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet, 46, 152–160.
  • Kim, S.H., Shi, Y., Hanson, K.A., Williams, L.M., Sakasai, R., Bowler, M.J., & Tibbetts, R.S. (2009). Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. J Biol Chem, 284, 8083–8092.
  • Kuo, P.H., Doudeva, L.G., Wang, Y.T., Shen, C.K., & Yuan, H.S. (2009). Structural insights into TDP-43 in nucleic-acid binding and domain interactions. Nucleic Acids Res, 37, 1799–1808.
  • Lacin, H., Zhu, Y., Wilson, B.A., & Skeath, J.B. (2014). Transcription factor expression uniquely identifies most postembryonic neuronal lineages in the Drosophila thoracic central nervous system. Development, 141, 1011–1021.
  • Lattante, S., Rouleau, G.A., & Kabashi, E. (2013). TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update. Hum Mutat, 34, 812–826.
  • Li, Y., Ray, P., Rao, E.J., Shi, C., Guo, W., Chen, X., et al. (2010). A Drosophila model for TDP-43 proteinopathy. Proc Natl Acad Sci U S A, 107, 3169–3174.
  • Liachko, N.F., Guthrie, C.R., & Kraemer, B.C. (2010). Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy. J Neurosci, 30, 16208–16219.
  • Lin, M.J., Cheng, C.W., & Shen, C.K. (2011). Neuronal function and dysfunction of Drosophila dTDP. PloS One, 6, e20371.
  • Ling, S.C., Albuquerque, C.P., Han, J.S., Lagier-Tourenne, C., Tokunaga, S., Zhou, H., & Cleveland, D.W. (2010). ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci U S A, 107, 13318–13323.
  • Ling, S.C., Polymenidou, M., & Cleveland, D.W. (2013). Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron, 79, 416–438.
  • Logroscino, G., Traynor, B.J., Hardiman, O., Chio, A., Mitchell, D., Swingler, R.J., et al. (2010). Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry, 81, 385–390.
  • Lu, Y., Ferris, J., & Gao, F.B. (2009). Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching. Mol Brain, 2, 30.
  • Mackenzie, I.R., Bigio, E.H., Ince, P.G., Geser, F., Neumann, M., Cairns, N.J., et al. (2007). Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol, 61, 427–434.
  • Mackenzie, I.R., Rademakers, R., & Neumann, M. (2010). TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol, 9, 995–1007.
  • Mizushima, N. (2007). Autophagy: process and function. Genes Dev, 21, 2861–2873.
  • Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., et al. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314, 130–133.
  • Odden, J.P., Holbrook, S., & Doe, C.Q. (2002). Drosophila HB9 is expressed in a subset of motoneurons and interneurons, where it regulates gene expression and axon pathfinding. J Neurosci, 22, 9143–9149.
  • Ou, S.H., Wu, F., Harrich, D., Garcia-Martinez, L.F., & Gaynor, R.B. (1995). Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J Virol, 69, 3584–3596.
  • Pircs, K., Nagy, P., Varga, A., Venkei, Z., Erdi, B., Hegedus, K., & Juhasz, G. (2012). Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila. PloS One, 7, e44214.
  • Polymenidou, M., Lagier-Tourenne, C., Hutt, K.R., Huelga, S.C., Moran, J., Liang, T.Y., et al. (2011). Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci, 14, 459–468.
  • Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., et al. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet, 36, 585–595.
  • Renton, A.E., Chio, A., & Traynor, B.J. (2014). State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci, 17, 17–23.
  • Rowland, L.P., & Shneider, N.A. (2001). Amyotrophic lateral sclerosis. N Engl J Med, 344, 1688–1700.
  • Salado, I.G., Redondo, M., Bello, M.L., Perez, C., Liachko, N.F., Kraemer, B.C., et al. (2014). Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J Med Chem, 57, 2755–2772.
  • Sarkar, S., Perlstein, E.O., Imarisio, S., Pineau, S., Cordenier, A., Maglathlin, R.L., et al. (2007). Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol, 3, 331–338.
  • Spilman, P., Podlutskaya, N., Hart, M.J., Debnath, J., Gorostiza, O., Bredesen, D., et al. (2010). Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PloS One, 5, e9979.
  • Strong, M.J., Volkening, K., Hammond, R., Yang, W., Strong, W., Leystra-Lantz, C., & Shoesmith, C. (2007). TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci, 35, 320–327.
  • Tatom, J.B., Wang, D.B., Dayton, R.D., Skalli, O., Hutton, M.L., Dickson, D.W., & Klein, R.L. (2009). Mimicking aspects of frontotemporal lobar degeneration and Lou Gehrig's disease in rats via TDP-43 overexpression. Mol Ther, 17, 607–613.
  • Tollervey, J.R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., et al. (2011). Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci, 14, 452–458.
  • Tooze, S.A., & Schiavo, G. (2008). Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration. Curr Opin Neurobiol, 18, 504–515.
  • Tsai, K.J., Yang, C.H., Fang, Y.H., Cho, K.H., Chien, W.L., Wang, W.T., et al. (2010). Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J Exp Med, 207, 1661–1673.
  • Uchida, A., Sasaguri, H., Kimura, N., Tajiri, M., Ohkubo, T., Ono, F., et al. (2012). Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43. Brain, 135, 833–846.
  • Vaccaro, A., Tauffenberger, A., Aggad, D., Rouleau, G., Drapeau, P., & Parker, J.A. (2012). Mutant TDP-43 and FUS cause age-dependent paralysis and neurodegeneration in C. elegans. PloS One, 7, e31321.
  • Van Langenhove, T., van der Zee, J., & Van Broeckhoven, C. (2012). The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann Med, 44, 817–828.
  • Voigt, A., Herholz, D., Fiesel, F.C., Kaur, K., Muller, D., Karsten, P., et al. (2010). TDP-43-mediated neuron loss in vivo requires RNA-binding activity. PloS one, 5, e12247.
  • Wang, H.Y., Wang, I.F., Bose, J., & Shen, C.K. (2004). Structural diversity and functional implications of the eukaryotic TDP gene family. Genomics, 83, 130–139.
  • Wang, I.F., Guo, B.S., Liu, Y.C., Wu, C.C., Yang, C.H., Tsai, K.J., & Shen, C.K. (2012). Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci U S A, 109, 15024–15029.
  • Wang, I.F., Tsai, K.J., & Shen, C.K. (2013). Autophagy activation ameliorates neuronal pathogenesis of FTLD-U mice: a new light for treatment of TARDBP/TDP-43 proteinopathies. Autophagy, 9, 239–240.
  • Wang, I.F., Wu, L.S., Chang, H.Y., & Shen, C.K. (2008a). TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J Neurochem, 105, 797–806.
  • Wang, I.F., Wu, L.S., & Shen, C.K. (2008b). TDP-43: an emerging new player in neurodegenerative diseases. Trends Mol Med, 14, 479–485.
  • Watson, M.R., Lagow, R.D., Xu, K., Zhang, B., & Bonini, N.M. (2008). A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1. J Biol Chem, 283, 24972–24981.
  • Wegorzewska, I., Bell, S., Cairns, N.J., Miller, T.M., & Baloh, R.H. (2009). TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A, 106, 18809–18814.
  • Wils, H., Kleinberger, G., Janssens, J., Pereson, S., Joris, G., Cuijt, I., et al. (2010). TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A, 107, 3858–3863.
  • Wu, L.S., Cheng, W.C., Hou, S.C., Yan, Y.T., Jiang, S.T., & Shen, C.K. (2010). TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis. Genesis, 48, 56–62.
  • Wu, L.S., Cheng, W.C., & Shen, C.K. (2012). Targeted depletion of TDP-43 expression in the spinal cord motor neurons leads to the development of amyotrophic lateral sclerosis-like phenotypes in mice. J Biol Chem, 287, 27335–27344.
  • Xu, Y.F., Gendron, T.F., Zhang, Y.J., Lin, W.L., D’Alton, S., Sheng, H., et al. (2010). Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci, 30, 10851–10859.
  • Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Wang, Z., & Le, W. (2011). Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy, 7, 412–425.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.