Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies

Manuela Neumann1, Linda K. Kwong2, Edward B. Lee2, Elisabeth Kremmer3, Andrew Flatley3, Yan Xu2, Mark S. Forman4, Dirk Troost5, Hans A. Kretzschmar6, John Q. Trojanowski2, Virginia M.‐Y. Lee2
1Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstr. 12, 8091, Zurich, Switzerland
2Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA
3Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Institute of Molecular Immunology, Munich, Germany
4Department of Experimental Medicine, Merck Research Laboratories, North Wales, USA
5Department of Neuropathology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
6Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany

Tóm tắt

Từ khóa


Tài liệu tham khảo

Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445. doi: 10.1002/ana.21154

Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611. doi: 10.1016/j.bbrc.2006.10.093

Baker M, Mackenzie IR, Pickering-Brown SM et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442:916–919. doi: 10.1038/nature05016

Buratti E, Baralle FE (2008) Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci 13:867–878. doi: 10.2741/2727

Buratti E, Dork T, Zuccato E, Pagani F, Romano M, Baralle FE (2001) Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 20:1774–1784. doi: 10.1093/emboj/20.7.1774

Cairns NJ, Bigio EH, Mackenzie IR et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114:5–22. doi: 10.1007/s00401-007-0237-2

Cairns NJ, Neumann M, Bigio EH et al (2007) TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 171:227–240. doi: 10.2353/ajpath.2007.070182

Cruts M, Gijselinck I, van der Zee J et al (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:920–924. doi: 10.1038/nature05017

Davidson Y, Kelley T, Mackenzie IR et al (2007) Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta Neuropathol 113:521–533. doi: 10.1007/s00401-006-0189-y

Dickson DW, Josephs KA, Amador-Ortiz C (2007) TDP-43 in differential diagnosis of motor neuron disorders. Acta Neuropathol 114:71–79. doi: 10.1007/s00401-007-0234-5

Fujiwara H, Hasegawa M, Dohmae N et al (2002) Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164. doi: 10.1038/ncb841

Geser F, Winton MJ, Kwong LK et al (2008) Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathol 115:133–145. doi: 10.1007/s00401-007-0257-y

Gitcho MA, Baloh RH, Chakraverty S et al (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63:535–538. doi: 10.1002/ana.21344

Hasegawa M, Arai T, Akiyama H et al (2007) TDP-43 is deposited in the Guam parkinsonism-dementia complex brains. Brain 130:1386–1394. doi: 10.1093/brain/awm065

Hasegawa M, Arai T, Nonaka T et al (2008) Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 64:60–70. doi: 10.1002/ana.21425

Igaz LM, Kwong LK, Xu Y et al (2008) Enrichment of C-terminal fragments in TAR DNA-binding protein-43 cytoplasmic inclusions in brain but not in spinal cord of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Am J Pathol 173:182–194. doi: 10.2353/ajpath.2008.080003

Inukai Y, Nonaka T, Arai T et al (2008) Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS. FEBS Lett 582:2899–2904. doi: 10.1016/j.febslet.2008.07.027

Kabashi E, Valdmanis PN, Dion P et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40:572–574. doi: 10.1038/ng.132

Kuhnlein P, Sperfeld AD, Vanmassenhove B et al (2008) Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. Arch Neurol 65:1185–1189. doi: 10.1001/archneur.65.9.1185

Kwong LK, Neumann M, Sampathu DM, Lee VM, Trojanowski JQ (2007) TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol 114:63–70. doi: 10.1007/s00401-007-0226-5

Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159. doi: 10.1146/annurev.neuro.24.1.1121

Mackenzie IR, Baborie A, Pickering-Brown S et al (2006) Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol 112:539–549. doi: 10.1007/s00401-006-0138-9

Mackenzie IR, Bigio EH, Ince PG et al (2007) Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 61:427–434. doi: 10.1002/ana.21147

Morita M, Al-Chalabi A, Andersen PM et al (2006) A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 66:839–844. doi: 10.1212/01.wnl.0000200048.53766.b4

Nakashima-Yasuda H, Uryu K, Robinson J et al (2007) Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 114:221–229. doi: 10.1007/s00401-007-0261-2

Neumann M, Kwong LK, Sampathu DM, Trojanowski JQ, Lee VM (2007) TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: protein misfolding diseases without amyloidosis. Arch Neurol 64:1388–1394. doi: 10.1001/archneur.64.10.1388

Neumann M, Kwong LK, Truax AC et al (2007) TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions. J Neuropathol Exp Neurol 66:177–183. doi: 10.1097/01.jnen.0000248554.45456.58

Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. doi: 10.1126/science.1134108

Olsen JV, Blagoev B, Gnad F et al (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635–648. doi: 10.1016/j.cell.2006.09.026

Ou SH, Wu F, Harrich D, Garcia-Martinez LF, Gaynor RB (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

Roeber S, Mackenzie IR, Kretzschmar HA, Neumann M (2008) TDP-43-negative FTLD-U is a significant new clinico-pathological subtype of FTLD. Acta Neuropathol 116:147–157. doi: 10.1007/s00401-008-0395-x

Rutherford NJ, Zhang YJ, Baker M et al (2008) Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet 4:e1000193. doi: 10.1371/journal.pgen.1000193

Sampathu DM, Neumann M, Kwong LK et al (2006) Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am J Pathol 169:1343–1352. doi: 10.2353/ajpath.2006.060438

Sreedharan J, Blair IP, Tripathi VB et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668–1672. doi: 10.1126/science.1154584

Uryu K, Nakashima-Yasuda H, Forman MS et al (2008) Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. J Neuropathol Exp Neurol 67:555–564. doi: 10.1097/NEN.0b013e31817713b5

Van Deerlin VM, Leverenz JB, Bekris LM et al (2008) TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 7:409–416. doi: 10.1016/S1474-4422(08)70071-1

Vance C, Al-Chalabi A, Ruddy D et al (2006) Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3. Brain 129:868–876. doi: 10.1093/brain/awl030

Watts GD, Wymer J, Kovach MJ et al (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 36:377–381. doi: 10.1038/ng1332

Yokoseki A, Shiga A, Tan CF et al (2008) TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 63:538–542. doi: 10.1002/ana.21392