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Articles, Neurobiology of Disease

Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies

Tara Vanderweyde, Haung Yu, Megan Varnum, Liqun Liu-Yesucevitz, Allison Citro, Tsuneya Ikezu, Karen Duff and Benjamin Wolozin
Journal of Neuroscience 13 June 2012, 32 (24) 8270-8283; DOI: https://doi.org/10.1523/JNEUROSCI.1592-12.2012
Tara Vanderweyde
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Haung Yu
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Megan Varnum
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Liqun Liu-Yesucevitz
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Allison Citro
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Tsuneya Ikezu
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Karen Duff
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Benjamin Wolozin
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Abstract

Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer's disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer's disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology.

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The Journal of Neuroscience: 32 (24)
Journal of Neuroscience
Vol. 32, Issue 24
13 Jun 2012
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Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies
Tara Vanderweyde, Haung Yu, Megan Varnum, Liqun Liu-Yesucevitz, Allison Citro, Tsuneya Ikezu, Karen Duff, Benjamin Wolozin
Journal of Neuroscience 13 June 2012, 32 (24) 8270-8283; DOI: 10.1523/JNEUROSCI.1592-12.2012

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Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies
Tara Vanderweyde, Haung Yu, Megan Varnum, Liqun Liu-Yesucevitz, Allison Citro, Tsuneya Ikezu, Karen Duff, Benjamin Wolozin
Journal of Neuroscience 13 June 2012, 32 (24) 8270-8283; DOI: 10.1523/JNEUROSCI.1592-12.2012
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