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Volumn 17, Issue 5, 2007, Pages 548-555

TDP-43: a novel neurodegenerative proteinopathy

Author keywords

[No Author keywords available]

Indexed keywords

DNA BINDING PROTEIN; TDP 43 PROTEIN; UNCLASSIFIED DRUG;

EID: 37549012160     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.conb.2007.08.005     Document Type: Review
Times cited : (107)

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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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    • Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations
    • 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.
    • 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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    • 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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    • TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations
    • 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.
    • 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.
    • (2007) J Neuropathol Exp Neurol , vol.66 , pp. 152-157
    • 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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    • 34249940732 scopus 로고    scopus 로고
    • TDP-43 in amyotrophic lateral sclerosis: pathophysiology or patho-babel?
    • This very interesting commentary questions whether the TDP-43 inclusions in ALS represent a pathological curiosity or have 'real pathophysiological relevance'. Time will tell.
    • 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.
    • (2007) Ann Neurol , vol.61 , pp. 382-384
    • Rothstein, J.D.1
  • 47
    • 34249751076 scopus 로고    scopus 로고
    • TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein
    • 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.
    • 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.
    • (2007) Mol Cell Neurosci , vol.35 , pp. 320-327
    • Strong, M.J.1    Volkening, K.2    Hammond, R.3    Yang, W.4    Strong, W.5    Leystra-Lantz, C.6    Shoesmith, C.7


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.