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Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
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Frontotemporal lobar degeneration: current concepts in the light of recent advances
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This is an outstanding review summarizing recent advances in genetics, biochemistry, and pathology in FTLD research.
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Kumar-Singh S., and Van B.C. Frontotemporal lobar degeneration: current concepts in the light of recent advances. Brain Pathol 17 (2007) 104-114. This is an outstanding review summarizing recent advances in genetics, biochemistry, and pathology in FTLD research.
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Brain Pathol
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Xiao S., McLean J., and Robertson J. Neuronal intermediate filaments and ALS: a new look at an old question. Biochim Biophys Acta 1762 (2006) 1001-1012
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This is a consensus paper on revised criteria for the neuropathological diagnosis of FTLD that incorporates recent advances in molecular genetics, biochemistry, and neuropathology including the identification of TDP-43 as the major disease protein in FTLD-U. The proposed classification scheme includes an algorithm for the neuropathological diagnosis of FTLD and is compared with the previous classification system described in 2001 [16].
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Cairns N.J., Bigio E.H., Mackenzie I.R.A., Neumann M., Lee V.M.Y., Hatanpaa K.J., White III C.L., Schneider J.A., Grinberg L.T., Halliday G., et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 1145 (2007) 5-22. This is a consensus paper on revised criteria for the neuropathological diagnosis of FTLD that incorporates recent advances in molecular genetics, biochemistry, and neuropathology including the identification of TDP-43 as the major disease protein in FTLD-U. The proposed classification scheme includes an algorithm for the neuropathological diagnosis of FTLD and is compared with the previous classification system described in 2001 [16].
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Cairns, N.J.1
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This study reports about the identification of PGRN mutations in patients with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and FTLD-U pathology. Interestingly, PGRN is located on chromosome 17q21, 1.7 Mb centromeric of MAPT, in which mutations are associated with FTDP-17 with tau pathology. All of the mutations in PGRN were predicted to cause premature termination of the coding sequence by nonsense-mediated decay of mutant mRNAs. In one large Belgian kindred, mutations were identified in the splice donor site of intron 0 causing loss of mutant transcript by nuclear degradation.
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Cruts M., Gijselinck I., van der Z.J., Engelborghs S., Wils H., Pirici D., Rademakers R., Vandenberghe R., Dermaut B., Martin J.J., et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442 (2006) 920-924. This study reports about the identification of PGRN mutations in patients with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and FTLD-U pathology. Interestingly, PGRN is located on chromosome 17q21, 1.7 Mb centromeric of MAPT, in which mutations are associated with FTDP-17 with tau pathology. All of the mutations in PGRN were predicted to cause premature termination of the coding sequence by nonsense-mediated decay of mutant mRNAs. In one large Belgian kindred, mutations were identified in the splice donor site of intron 0 causing loss of mutant transcript by nuclear degradation.
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Nature
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This study reports about the first identification of PGRN mutations in patients with FTDP-17 and FTLD-U pathology. Interestingly, PGRN is located on chromosome 17q21, 1.7 Mb centromeric of MAPT, and encodes for 68-kDa secreted growth factor. All of the mutations in PGRN were predicted to cause premature termination of the coding sequence by nonsense-mediated decay of mutant mRNAs. The authors propose that the mutations cause disease by haploinsufficiency.
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Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J., Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick A.D., Rollinson S., et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442 (2006) 916-919. This study reports about the first identification of PGRN mutations in patients with FTDP-17 and FTLD-U pathology. Interestingly, PGRN is located on chromosome 17q21, 1.7 Mb centromeric of MAPT, and encodes for 68-kDa secreted growth factor. All of the mutations in PGRN were predicted to cause premature termination of the coding sequence by nonsense-mediated decay of mutant mRNAs. The authors propose that the mutations cause disease by haploinsufficiency.
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Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein
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This study is the first comprehensive description of the neuropathology of 'Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia' (IBMPFD) caused by mutations in VCP. The CNS pathology in IBMPFD is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial FTLD-U, that is, type 4 (Figure 1).
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Forman M.S., Mackenzie I.R., Cairns N.J., Swanson E., Boyer P.J., Drachman D.A., Jhaveri B.S., Karlawish J.H., Pestronk A., Smith T.W., et al. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol 65 (2006) 571-581. This study is the first comprehensive description of the neuropathology of 'Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia' (IBMPFD) caused by mutations in VCP. The CNS pathology in IBMPFD is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial FTLD-U, that is, type 4 (Figure 1).
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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
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In this study, the authors generated novel monoclonal antibodies to the ubiquitin pathology of FTLD-U leading to the identification of TDP-43 as the major disease protein. Antibodies to TDP-43 did not detect the pathology in a variety of other neurodegenerative characterized by inclusion pathology. However, TDP-43 was also detected in the UBI of ALS, providing the first molecular link between these two neurodegenerative disorders. Pathological TDP-43 was abnormally phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments from affected CNS regions.
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Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., Micsenyi M.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314 (2006) 130-133. In this study, the authors generated novel monoclonal antibodies to the ubiquitin pathology of FTLD-U leading to the identification of TDP-43 as the major disease protein. Antibodies to TDP-43 did not detect the pathology in a variety of other neurodegenerative characterized by inclusion pathology. However, TDP-43 was also detected in the UBI of ALS, providing the first molecular link between these two neurodegenerative disorders. Pathological TDP-43 was abnormally phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments from affected CNS regions.
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To investigate the function of TDP-43, this study describes the cloning and characterization of TDP-43 homologs from Drosophila melanogaster and Caenorhabditis elegans. The proteins from human, fly, and worm showed striking similarities in their nucleic acid-binding specificity. However, differences in the structure of the glycine-rich C-terminal domain between human, fly, and worm implicated this domain in the splicing regulatory function of the protein.
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This study demonstrated that the C-terminal domain of TDP-43 is capable of binding directly to several proteins of the hnRNP family with well-defined splicing inhibitory activity including hnRNP A2/B1 and hnRNP A1. TDP-43 protein lacking the C-terminal region did not inhibit splicing because hnRNP-rich complexes were not formed at the earliest stages of spliceosomal assembly.
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Buratti E., Brindisi A., Giombi M., Tisminetzky S., Ayala Y.M., and Baralle F.E. TDP-43 binds heterogeneous nuclear ribonucleoprotein 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 (2005) 37572-37584. This study demonstrated that the C-terminal domain of TDP-43 is capable of binding directly to several proteins of the hnRNP family with well-defined splicing inhibitory activity including hnRNP A2/B1 and hnRNP A1. TDP-43 protein lacking the C-terminal region did not inhibit splicing because hnRNP-rich complexes were not formed at the earliest stages of spliceosomal assembly.
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This is a large survey study on 193 cases of familial and sporadic FTLD. The study confirmed the specificity of TDP-43 for the ubiquitin pathology in FTLD-U but not in other pathologies associated with FTLD including Pick's disease, corticobasal degeneration, progressive supranuclear palsy, and FTDP-17 because of MAPT gene mutations. The study also validated the classification scheme of FTLD-U and correlated the pathological subtypes with specific genetic abnormalities.
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Cairns N.J., Neumann M., Bigio E.H., Holm I.E., Troost D., Hatanpaa K.J., Foong C., White III C.L., Schneider J.A., Kretzschmar H.A., et al. TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 171 (2007) 227-240. This is a large survey study on 193 cases of familial and sporadic FTLD. The study confirmed the specificity of TDP-43 for the ubiquitin pathology in FTLD-U but not in other pathologies associated with FTLD including Pick's disease, corticobasal degeneration, progressive supranuclear palsy, and FTDP-17 because of MAPT gene mutations. The study also validated the classification scheme of FTLD-U and correlated the pathological subtypes with specific genetic abnormalities.
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Hasegawa, M.2
Akiyama, H.3
Ikeda, K.4
Nonaka, T.5
Mori, H.6
Mann, D.7
Tsuchiya, K.8
Yoshida, M.9
Hashizume, Y.10
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33
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34249712890
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TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations
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Seelaar H., Schelhaas H.J., Azmani A., Kusters B., Rosso S., Majoor-Krakauer D., de Rijik M.C., Rizzu P., ten B.M., van Doorn P.A., et al. TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations. Brain 130 (2007) 1375-1385
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(2007)
Brain
, vol.130
, pp. 1375-1385
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Seelaar, H.1
Schelhaas, H.J.2
Azmani, A.3
Kusters, B.4
Rosso, S.5
Majoor-Krakauer, D.6
de Rijik, M.C.7
Rizzu, P.8
ten, B.M.9
van Doorn, P.A.10
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34
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34248562396
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Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with ubiquitin-positive inclusions
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Higashi S., Iseki E., Yamamoto R., Minegishi M., Hino H., Fujisawa K., Togo T., Katsuse O., Uchikado H., Furukawa Y., et al. Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with ubiquitin-positive inclusions. Neurosci Lett 419 (2007) 213-218
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(2007)
Neurosci Lett
, vol.419
, pp. 213-218
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Higashi, S.1
Iseki, E.2
Yamamoto, R.3
Minegishi, M.4
Hino, H.5
Fujisawa, K.6
Togo, T.7
Katsuse, O.8
Uchikado, H.9
Furukawa, Y.10
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35
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34247606414
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TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation
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In this study, the brains and spinal cords from four cases of fALS because of SOD1 gene mutations was examined by TDP-43 immunohistochemistry and compared with sporadic ALS and fALS without SOD1 mutations. The UBI in both sporadic ALS and non-SOD1 fALS were TDP-43-immunoreactive. In contrast, the ubiquitin pathology in fALS with SOD1 gene mutations was not detected with antibodies to TDP-43. These data support the hypothesis that ALS because of SOD1 mutations reflects a disease pathway distinct from the sporadic disease counterpart.
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Tan C.F., Eguchi H., Tagawa A., Onodera O., Iwasaki T., Tsujino A., Nishizawa M., Kakita A., and Takahashi H. TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation. Acta Neuropathol 113 (2007) 535-542. In this study, the brains and spinal cords from four cases of fALS because of SOD1 gene mutations was examined by TDP-43 immunohistochemistry and compared with sporadic ALS and fALS without SOD1 mutations. The UBI in both sporadic ALS and non-SOD1 fALS were TDP-43-immunoreactive. In contrast, the ubiquitin pathology in fALS with SOD1 gene mutations was not detected with antibodies to TDP-43. These data support the hypothesis that ALS because of SOD1 mutations reflects a disease pathway distinct from the sporadic disease counterpart.
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(2007)
Acta Neuropathol
, vol.113
, pp. 535-542
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Tan, C.F.1
Eguchi, H.2
Tagawa, A.3
Onodera, O.4
Iwasaki, T.5
Tsujino, A.6
Nishizawa, M.7
Kakita, A.8
Takahashi, H.9
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36
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34249946466
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Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations
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This is a survey study investigating TDP-43 using both biochemistry and immunohistochemistry in a large series of ALS cases (n = 111) including fALS with and without SOD1 gene mutations. The UBI of all cases of sporadic ALS, ALS with dementia, and SOD1-negative fALS were immunoreactive with antibodies to TDP-43 including the detection of oligodendroglial inclusions that were not appreciated with immunostaining for ubiquitin. By contrast, the UBI of fALS with SOD1 gene mutations were not detected with TDP-43 immunohistochemistry. These findings implicate TDP-43 in the pathogenesis of ALS and support the hypothesis that fALS caused by SOD1 gene mutations may result from a different disease pathway that also affects motor neurons.
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Mackenzie I.R., Bigio E.H., Ince P.G., Geser F., Neumann M., Cairns N.J., Kwong L.K., Forman M.S., Ravits J., Stewart H., et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 61 (2007) 427-434. This is a survey study investigating TDP-43 using both biochemistry and immunohistochemistry in a large series of ALS cases (n = 111) including fALS with and without SOD1 gene mutations. The UBI of all cases of sporadic ALS, ALS with dementia, and SOD1-negative fALS were immunoreactive with antibodies to TDP-43 including the detection of oligodendroglial inclusions that were not appreciated with immunostaining for ubiquitin. By contrast, the UBI of fALS with SOD1 gene mutations were not detected with TDP-43 immunohistochemistry. These findings implicate TDP-43 in the pathogenesis of ALS and support the hypothesis that fALS caused by SOD1 gene mutations may result from a different disease pathway that also affects motor neurons.
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(2007)
Ann Neurol
, vol.61
, pp. 427-434
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Mackenzie, I.R.1
Bigio, E.H.2
Ince, P.G.3
Geser, F.4
Neumann, M.5
Cairns, N.J.6
Kwong, L.K.7
Forman, M.S.8
Ravits, J.9
Stewart, H.10
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37
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34247123666
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TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions
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This study demonstrates abundant TDP-43-immunoreactive white matter pathology as a characteristic disease feature in 38 FTLD-U cases including 3 with PGRN mutations. The white matter inclusions are most probably oligodendrocytes based on morphology and double-labeling studies. These findings expanded the spectrum of TDP-43 pathology in FTLD-U and implicated white matter disease in the neurodegenerative process.
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Neumann M., Kwong L.K., Truax A.C., Vanmassenhove B., Kretzschmar H.A., Van D.V., Clark C.M., Grossman M., Miller B.L., Trojanowski J.Q., et al. TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions. J Neuropathol Exp Neurol 66 (2007) 177-183. This study demonstrates abundant TDP-43-immunoreactive white matter pathology as a characteristic disease feature in 38 FTLD-U cases including 3 with PGRN mutations. The white matter inclusions are most probably oligodendrocytes based on morphology and double-labeling studies. These findings expanded the spectrum of TDP-43 pathology in FTLD-U and implicated white matter disease in the neurodegenerative process.
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(2007)
J Neuropathol Exp Neurol
, vol.66
, pp. 177-183
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Neumann, M.1
Kwong, L.K.2
Truax, A.C.3
Vanmassenhove, B.4
Kretzschmar, H.A.5
Van, D.V.6
Clark, C.M.7
Grossman, M.8
Miller, B.L.9
Trojanowski, J.Q.10
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38
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33846815066
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TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations
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This study analyzed the ubiquitin pathology in IBMPFD associated with VCP gene mutations. The NII and DN were labeled with antibodies to TDP-43 leading to the hypothesis that VCP mutations lead to a dominant-negative loss or alteration of VCP function culminating in impaired degradation of TDP-43. This study supports the central role of TDP-43 as a common pathological substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations.
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Neumann M., Mackenzie I.R., Cairns N.J., Boyer P.J., Markesbery W.R., Smith C.D., Taylor J.P., Kretzschmar H.A., Kimonis V.E., and Forman M.S. TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 66 (2007) 152-157. This study analyzed the ubiquitin pathology in IBMPFD associated with VCP gene mutations. The NII and DN were labeled with antibodies to TDP-43 leading to the hypothesis that VCP mutations lead to a dominant-negative loss or alteration of VCP function culminating in impaired degradation of TDP-43. This study supports the central role of TDP-43 as a common pathological substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations.
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(2007)
J Neuropathol Exp Neurol
, vol.66
, pp. 152-157
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Neumann, M.1
Mackenzie, I.R.2
Cairns, N.J.3
Boyer, P.J.4
Markesbery, W.R.5
Smith, C.D.6
Taylor, J.P.7
Kretzschmar, H.A.8
Kimonis, V.E.9
Forman, M.S.10
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39
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34249313704
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Lack of TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with ALS
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Robertson J., Sanelli T., Xiao S., Yang W., Horne P., Hammond R., Pioro E.P., and Strong M.J. Lack of TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with ALS. Neurosci Lett 420 (2007) 128-132
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(2007)
Neurosci Lett
, vol.420
, pp. 128-132
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Robertson, J.1
Sanelli, T.2
Xiao, S.3
Yang, W.4
Horne, P.5
Hammond, R.6
Pioro, E.P.7
Strong, M.J.8
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40
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36949036676
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Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam
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Geser F., Winton M.J., Kwong L.K., Xu Y., Xie S.X., Igaz L.M., Garruto R.M., Perl D.P., Galasko D., Lee V.M.Y., et al. Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathol 115 (2008) 133-145
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(2008)
Acta Neuropathol
, vol.115
, pp. 133-145
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Geser, F.1
Winton, M.J.2
Kwong, L.K.3
Xu, Y.4
Xie, S.X.5
Igaz, L.M.6
Garruto, R.M.7
Perl, D.P.8
Galasko, D.9
Lee, V.M.Y.10
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41
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34249709931
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TDP-43 is deposited in the Guam parkinsonism-dementia complex brains
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Hasegawa M., Arai T., Akiyama H., Nonaka T., Mori H., Hashimoto T., Yamazaki M., and Oyanagi K. TDP-43 is deposited in the Guam parkinsonism-dementia complex brains. Brain 130 (2007) 1386-1394
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(2007)
Brain
, vol.130
, pp. 1386-1394
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Hasegawa, M.1
Arai, T.2
Akiyama, H.3
Nonaka, T.4
Mori, H.5
Hashimoto, T.6
Yamazaki, M.7
Oyanagi, K.8
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42
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34249940732
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TDP-43 in amyotrophic lateral sclerosis: pathophysiology or patho-babel?
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This very interesting commentary questions whether the TDP-43 inclusions in ALS represent a pathological curiosity or have 'real pathophysiological relevance'. Time will tell.
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Rothstein J.D. TDP-43 in amyotrophic lateral sclerosis: pathophysiology or patho-babel?. Ann Neurol 61 (2007) 382-384. This very interesting commentary questions whether the TDP-43 inclusions in ALS represent a pathological curiosity or have 'real pathophysiological relevance'. Time will tell.
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(2007)
Ann Neurol
, vol.61
, pp. 382-384
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Rothstein, J.D.1
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43
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34249658365
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A novel progranulin mutation associated with variable clinical presentation and tau, TDP43 and alpha-synuclein pathology
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Leverenz J.B., Yu C.E., Montine T.J., Steinbart E., Bekris L.M., Zabetian C., Kwong L.K., Lee V.M.Y., Schellenberg G.D., and Bird T.D. A novel progranulin mutation associated with variable clinical presentation and tau, TDP43 and alpha-synuclein pathology. Brain 130 (2007) 1360-1374
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(2007)
Brain
, vol.130
, pp. 1360-1374
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Leverenz, J.B.1
Yu, C.E.2
Montine, T.J.3
Steinbart, E.4
Bekris, L.M.5
Zabetian, C.6
Kwong, L.K.7
Lee, V.M.Y.8
Schellenberg, G.D.9
Bird, T.D.10
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44
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34547733547
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Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
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Nakashima-Yasuda H., Uryu K., Robinson J., Xie S.X., Hurtig H., Duda J.E., Arnold S.E., Siderowf A., Grossman M., Leverenz J.B., et al. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 114 (2007) 221-229
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(2007)
Acta Neuropathol
, vol.114
, pp. 221-229
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Nakashima-Yasuda, H.1
Uryu, K.2
Robinson, J.3
Xie, S.X.4
Hurtig, H.5
Duda, J.E.6
Arnold, S.E.7
Siderowf, A.8
Grossman, M.9
Leverenz, J.B.10
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45
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34249949338
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TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
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•].
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•].
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(2007)
Ann Neurol
, vol.61
, pp. 435-445
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Amador-Ortiz, C.1
Lin, W.L.2
Ahmed, Z.3
Personett, D.4
Davies, P.5
Duara, R.6
Graff-Radford, N.R.7
Hutton, M.L.8
Dickson, D.W.9
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46
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34247868841
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TDP-43 gene analysis in frontotemporal lobar degeneration
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Rollinson S., Snowden J.S., Neary D., Morrison K.E., Mann D.M., and Pickering-Brown S.M. TDP-43 gene analysis in frontotemporal lobar degeneration. Neurosci Lett 419 (2007) 1-4
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(2007)
Neurosci Lett
, vol.419
, pp. 1-4
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Rollinson, S.1
Snowden, J.S.2
Neary, D.3
Morrison, K.E.4
Mann, D.M.5
Pickering-Brown, S.M.6
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47
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34249751076
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TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein
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This study demonstrated that TDP-43 stabilizes low molecular weight neurofilament mRNA through a direct interaction with the 3′UTR. Thus, the sequestration of TDP-43 in cytosolic inclusions could contribute to the formation of neurofilament aggregates by destabilizing low molecular weight neurofilament message thereby altering the stoichiometry of neurofilament subunits in neurons.
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Strong M.J., Volkening K., Hammond R., Yang W., Strong W., Leystra-Lantz C., and Shoesmith C. TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci 35 (2007) 320-327. This study demonstrated that TDP-43 stabilizes low molecular weight neurofilament mRNA through a direct interaction with the 3′UTR. Thus, the sequestration of TDP-43 in cytosolic inclusions could contribute to the formation of neurofilament aggregates by destabilizing low molecular weight neurofilament message thereby altering the stoichiometry of neurofilament subunits in neurons.
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(2007)
Mol Cell Neurosci
, vol.35
, pp. 320-327
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Strong, M.J.1
Volkening, K.2
Hammond, R.3
Yang, W.4
Strong, W.5
Leystra-Lantz, C.6
Shoesmith, C.7
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48
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34247595383
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Absence of heterogeneous nuclear ribonucleoproteins and survival motor neuron protein in TDP-43 positive inclusions in frontotemporal lobar degeneration
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Neumann M., Igaz L.M., Kwong L.K., Nakashima-Yasuda H., Kolb S.J., Dreyfuss G., Kretzschmar H.A., Trojanowski J.Q., and Lee V.M.Y. Absence of heterogeneous nuclear ribonucleoproteins and survival motor neuron protein in TDP-43 positive inclusions in frontotemporal lobar degeneration. Acta Neuropathol (Berl) 113 (2007) 543-548
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(2007)
Acta Neuropathol (Berl)
, vol.113
, pp. 543-548
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Neumann, M.1
Igaz, L.M.2
Kwong, L.K.3
Nakashima-Yasuda, H.4
Kolb, S.J.5
Dreyfuss, G.6
Kretzschmar, H.A.7
Trojanowski, J.Q.8
Lee, V.M.Y.9
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