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2,922 results on '"Lee, Virginia M-Y."'

211. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis

Author

Van Deerlin, Vivianna M, Leverenz, James B, Bekris, Lynn M, Bird, Thomas D, Yuan, Wuxing, Elman, Lauren B, Clay, Dana, Wood, Elisabeth McCarty, Chen-Plotkin, Alice S, Martinez-Lage, Maria, Steinbart, Ellen, McCluskey, Leo, Grossman, Murray, Neumann, Manuela, Wu, I-Lin, Yang, Wei-Shiung, Kalb, Robert, Galasko, Douglas R, Montine, Thomas J, Trojanowski, John Q, Lee, Virginia M-Y, Schellenberg, Gerard D, and Yu, Chang-En

Published
2008
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213. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice

Author

Igaz, Lionel M., Kwong, Linda K., Lee, Edward B., Chen-Plotkin, Alice, Swanson, Eric, Unger, Travis, Malunda, Joe, Xu, Yan, Winton, Matthew J., Trojanowski, John Q., and Lee, Virginia M.-y.

Subjects
Physiological aspects, Genetic aspects, Protein binding -- Physiological aspects, Amyotrophic lateral sclerosis -- Physiological aspects -- Genetic aspects, Gene expression -- Physiological aspects
Abstract

Introduction Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are characterized by the presence of ubiquitin-positive inclusions (1). These inclusions are found in the brain and spinal cord of [...], Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are characterized by cytoplasmic protein aggregates in the brain and spinal cord that include TAR-DNA binding protein 43 (TDP-43). TDP-43 is normally localized in the nucleus with roles in the regulation of gene expression, and pathological cytoplasmic aggregates are associated with depletion of nuclear protein. Here, we generated transgenic mice expressing human TDP-43 with a defective nuclear localization signal in the forebrain (hTDP-43-ΔNLS), and compared them with mice expressingWT hTDP-43 (hTDP-43-WT) to determine the effects of mislocalized cytoplasmic TDP-43 on neuronal viability. Expression of either hTDP-43-ΔNLS or hTDP-43-WT led to neuron loss in selectively vulnerable forebrain regions, corticospinal tract degeneration, and motor spasticity recapitulating key aspects of FTLD and primary lateral sclerosis. Only rare cytoplasmic phosphorylated and ubiquitinated TDP-43 inclusions were seen in hTDP-43-ΔNLS mice, suggesting that cytoplasmic inclusions were not required to induce neuronal death. Instead, neurodegeneration in hTDP-43 and hTDP-43-ΔNLS-expressing neurons was accompanied by a dramatic downregulation of the endogenous mouse TDP-43. Moreover, mice expressing hTDP-43-ΔNLS exhibited profound changes in gene expression in cortical neurons. Our data suggest that perturbation of endogenous nuclear TDP-43 results in loss of normal TDP-43 function(s) and gene regulatory pathways, culminating in degeneration of selectively vulnerable affected neurons.

Published
2011
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223. Additional file 1 of Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery

Author

Hunter, Mandana, Spiller, Krista J., Dominique, Myrna A., Xu, Hong, Hunter, Francis W., Fang, Terry C., Canter, Rebecca G., Roberts, Christopher J., Ransohoff, Richard M., Trojanowski, John Q., and Lee, Virginia M.-Y.

Subjects
Data_FILES
Abstract

Additional file 1. Supplemental figures and tables.

Published
2021
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224. Additional file 1 of Effects of microglial depletion and TREM2 deficiency on Aβ plaque burden and neuritic plaque tau pathology in 5XFAD mice

Author

Delizannis, Argyro Thalia, Nonneman, Annelies, Tsering, Wangchen, De Bondt, An, Van den Wyngaert, Ilse, Zhang, Bin, Meymand, Emily, Olufemi, Modupe F., Koivula, Pyry, Maimaiti, Shaniya, Trojanowski, John Q., Lee, Virginia M.-Y., and Brunden, Kurt R.

Subjects
Data_FILES
Abstract

Additional file 1. Supplemental figures and tables.

Published
2021
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228. Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy

Author

Lim, Jormay, Balastik, Martin, Lee, Tae Ho, Nakamura, Kazuhiro, Liou, Yih-Cherng, Sun, Anyang, Finn, Greg, Pastorino, Lucia, Lee, Virginia M.-Y., and Lu, Kun Ping

Subjects
Development and progression, Research, Genetic aspects, Risk factors, Health aspects, Gene mutation -- Health aspects -- Research -- Genetic aspects, Neurodegenerative diseases -- Risk factors -- Genetic aspects -- Development and progression -- Research, Gene mutations -- Health aspects -- Research -- Genetic aspects, Nervous system -- Degeneration
Abstract

Introduction Tau-related phenotypes are prominent common features of many neurodegenerative diseases, called tauopathies, that include Alzheimer disease (AD), frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), corticobasal degeneration, progressive [...], Tau pathology is a hallmark of many neurodegenerative diseases including Alzheimer disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Genetic tau mutations can cause FTDP-17, and mice overexpressing tau mutants such as P301L tau are used as AD models. However, since no tau mutations are found in AD, it remains unclear how appropriate tau mutant mice are as an AD model. The prolyl isomerase Pin1 binds and isomerizes tau and has been implicated in protecting against neurodegeneration, but whether such Pin1 regulation is affected by tau mutations is unknown. Consistent with earlier findings that Pin1 KO induces tauopathy, here we demonstrate that Pin1 knockdown or KO increased WT tau protein stability in vitro and in mice and that Pin1 overexpression suppressed the tauopathy phenotype in WT tau transgenic mice. Unexpectedly, Pin1 knockdown or KO decreased P301L tau protein stability and abolished its robust tauopathy phenotype in mice. In contrast, Pin1 overexpression exacerbated the tauopathy phenotype in P301L tau mice. Thus, Pin1 has opposite effects on the tauopathy phenotype depending on whether the tau is WT or a P301L mutant, indicating the need for disease-specific therapies for tauopathies.

Published
2008

229. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases

Author

Nakashima-Yasuda, Hanae, Uryu, Kunihiro, Robinson, John, Xie, Sharon X., Hurtig, Howard, Duda, John E., Arnold, Steven E., Siderowf, Andrew, Grossman, Murray, Leverenz, James B., Woltjer, Randy, Lopez, Oscar L., Hamilton, Ronald, Tsuang, Debby W., Galasko, Douglas, Masliah, Eliezer, Kaye, Jeffrey, Clark, Christopher M., Montine, Thomas J., Lee, Virginia M. -Y., and Trojanowski, John Q.

Published
2007
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230. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration

Author

Cairns, Nigel J., Bigio, Eileen H., Mackenzie, Ian R. A., Neumann, Manuela, Lee, Virginia M.-Y., Hatanpaa, Kimmo J., White, III, Charles L., Schneider, Julie A., Grinberg, Lea Tenenholz, Halliday, Glenda, Duyckaerts, Charles, Lowe, James S., Holm, Ida E., Tolnay, Markus, Okamoto, Koichi, Yokoo, Hideaki, Murayama, Shigeo, Woulfe, John, Munoz, David G., Dickson, Dennis W., Ince, Paul G., Trojanowski, John Q., and Mann, David M. A.

Published
2007
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241. TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions

Author

Cairns, Nigel J., Neumann, Manuela, Bigio, Eileen H., Holm, Ida E., Troost, Dirk, Hatanpaa, Kimmo J., Foong, Chan, White, Charles L., III, Schneider, Julie A., Kretzschmar, Hans A., Carter, Deborah, Taylor-Reinwald, Lisa, Paulsmeyer, Katherine, Strider, Jeffrey, Gitcho, Michael, Goate, Alison M., Morris, John C., Mishra, Manjari, Kwong, Linda K., Stieber, Anna, Xu, Yan, Forman, Mark S., Trojanowski, John Q., Lee, Virginia M.-Y., and Mackenzie, Ian R.A.

Published
2007
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246. Computational modeling of tau pathology spread reveals patterns of regional vulnerability and the impact of a genetic risk factor

Author

Cornblath, Eli J., primary, Li, Howard L., additional, Changolkar, Lakshmi, additional, Zhang, Bin, additional, Brown, Hannah J., additional, Gathagan, Ronald J., additional, Olufemi, Modupe F., additional, Trojanowski, John Q., additional, Bassett, Danielle S., additional, Lee, Virginia M. Y., additional, and Henderson, Michael X., additional

Published
2021
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249. Environmental enrichment reduces A-beta levels and amyloid deposition in transgenic mice

Author

Lazarov, Orly, Robinson, John, Ya-ping Tang, Hariston, IIana S., Zelka Korade-Mirnics, Lee, Virginia M. Y., Hersh, Louis B., Sapolsky, Robert M., Mirnics, Karoly, and Sisodia, Sangram S.

Subjects
Biological sciences
Abstract

Studies provide evidence that environmental enrichment leads to reductions in steady-state levels of cerebral amyloid-beta peptides and amyloid deposition and selective upregulation in levels of specific transcripts in brains of trangenic mice. The enzymatic activity of an amyloid-beta degrading endopeptidase, nephrilysin, is elevated in the brains of 'enriched' mice and inversely correlated with amyloid burden.

Published
2005

250. BACE overexpression alters the subcellular processing of APP and inhibits A[beta] deposition in vivo

Author

Lee, Edward B., Zhang, Bin, Liu, Kangning, Greenbaum, Eric A., Doms, Robert W., Trojanowski, John Q., and Lee, Virginia M.-Y.

Subjects
Amyloid beta-protein -- Research, Amyloid beta-protein -- Physiological aspects, Cytology -- Research, Biological sciences
Abstract

Introducing mutations within the amyloid precursor protein (APP) that affect [beta]- and [gamma]-secretase cleavages results in amyloid plaque formation in vivo. However, the relationship between [beta]-amyloid deposition and the subcellular site of A[beta] production is unknown. To determine the effect of increasing [beta]-secretase (BACE) activity on A[beta] deposition, we generated transgenic mice overexpressing human BACE. Although modest overexpression enhanced amyloid deposition, high BACE overexpression inhibited amyloid formation despite increased [beta]-cleavage of APP. However, high BACE expression shifted the subcellular location of APP cleavage to the neuronal perikarya early in the secretory pathway. These results suggest that the production, clearance, and aggregation of A[beta] peptides are highly dependent on the specific neuronal subcellular domain wherein A[beta] is generated and highlight the importance of perikaryal versus axonal APP proteolysis in the development of A[beta] amyloid pathology in Alzheimer's disease.

Published
2005

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