Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

Daniel J. Apicco; Peter E.A. Ash; Brandon Maziuk; Chelsey Leblang; Maria Medalla; Ali Al Abdullatif; Antonio Ferragud; Emily Botelho; Heather I. Ballance; Uma Dhawan; Samantha Boudeau; Anna Lourdes Cruz; Daniel Kashy; Aria Wong; Lisa R. Goldberg; Neema Yazdani; Cheng Zhang; Choong Y. Ung; Yorghos Tripodis; Nicholas M. Kanaan; Tsuneya Ikezu; Pietro Cottone; John Leszyk; Hu Li; Jennifer Luebke; Camron D. Bryant; Benjamin Wolozin

doi:10.1038/s41593-017-0022-z

Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

Daniel J. Apicco, Peter E.A. Ash, Brandon Maziuk, Chelsey Leblang, Maria Medalla, Ali Al Abdullatif, Antonio Ferragud, Emily Botelho, Heather I. Ballance, Uma Dhawan, Samantha Boudeau, Anna Lourdes Cruz, Daniel Kashy, Aria Wong, Lisa R. Goldberg, Neema Yazdani, Cheng Zhang, Choong Y. Ung, Yorghos Tripodis, Nicholas M. KanaanTsuneya Ikezu, Pietro Cottone, John Leszyk, Hu Li, Jennifer Luebke, Camron D. Bryant, Benjamin Wolozin

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.

Original language	English (US)
Pages (from-to)	72-82
Number of pages	11
Journal	Nature Neuroscience
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/s41593-017-0022-z
State	Published - Jan 1 2018

ASJC Scopus subject areas

Neuroscience(all)

Access to Document

10.1038/s41593-017-0022-z

Cite this

Apicco, D. J., Ash, P. E. A., Maziuk, B., Leblang, C., Medalla, M., Al Abdullatif, A., Ferragud, A., Botelho, E., Ballance, H. I., Dhawan, U., Boudeau, S., Cruz, A. L., Kashy, D., Wong, A., Goldberg, L. R., Yazdani, N., Zhang, C., Ung, C. Y., Tripodis, Y., ... Wolozin, B. (2018). Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. Nature Neuroscience, 21(1), 72-82. https://doi.org/10.1038/s41593-017-0022-z

Apicco, DJ, Ash, PEA, Maziuk, B, Leblang, C, Medalla, M, Al Abdullatif, A, Ferragud, A, Botelho, E, Ballance, HI, Dhawan, U, Boudeau, S, Cruz, AL, Kashy, D, Wong, A, Goldberg, LR, Yazdani, N, Zhang, C, Ung, CY, Tripodis, Y, Kanaan, NM, Ikezu, T, Cottone, P, Leszyk, J, Li, H, Luebke, J, Bryant, CD & Wolozin, B 2018, 'Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo', Nature Neuroscience, vol. 21, no. 1, pp. 72-82. https://doi.org/10.1038/s41593-017-0022-z

@article{637daf9af3b4425ebb8abbaa79e3d1b9,

title = "Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo",

abstract = "Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.",

author = "Apicco, {Daniel J.} and Ash, {Peter E.A.} and Brandon Maziuk and Chelsey Leblang and Maria Medalla and {Al Abdullatif}, Ali and Antonio Ferragud and Emily Botelho and Ballance, {Heather I.} and Uma Dhawan and Samantha Boudeau and Cruz, {Anna Lourdes} and Daniel Kashy and Aria Wong and Goldberg, {Lisa R.} and Neema Yazdani and Cheng Zhang and Ung, {Choong Y.} and Yorghos Tripodis and Kanaan, {Nicholas M.} and Tsuneya Ikezu and Pietro Cottone and John Leszyk and Hu Li and Jennifer Luebke and Bryant, {Camron D.} and Benjamin Wolozin",

note = "Funding Information: We thank P. Davies (Feinstein Institute) for provision of CP13 and PHF1 antibodies. We thank the following funding agencies for their support: B.W. received support from the NIH (AG050471, NS089544 and ES020395), BrightFocus Foundation, Alzheimer Association, Cure Alzheimer{\textquoteright}s Fund and the Thome Medical Foundation; U.D. received support from a UGC-Raman Fellowship and the Government of India; T.I. received support from the NIH (R01 AG054199); H.L. received support from the Paul F. Glenn Foundation. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2018",

month = jan,

day = "1",

doi = "10.1038/s41593-017-0022-z",

language = "English (US)",

volume = "21",

pages = "72--82",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

AU - Apicco, Daniel J.

AU - Ash, Peter E.A.

AU - Maziuk, Brandon

AU - Leblang, Chelsey

AU - Medalla, Maria

AU - Al Abdullatif, Ali

AU - Ferragud, Antonio

AU - Botelho, Emily

AU - Ballance, Heather I.

AU - Dhawan, Uma

AU - Boudeau, Samantha

AU - Cruz, Anna Lourdes

AU - Kashy, Daniel

AU - Wong, Aria

AU - Goldberg, Lisa R.

AU - Yazdani, Neema

AU - Zhang, Cheng

AU - Ung, Choong Y.

AU - Tripodis, Yorghos

AU - Kanaan, Nicholas M.

AU - Ikezu, Tsuneya

AU - Cottone, Pietro

AU - Leszyk, John

AU - Li, Hu

AU - Luebke, Jennifer

AU - Bryant, Camron D.

AU - Wolozin, Benjamin

N1 - Funding Information: We thank P. Davies (Feinstein Institute) for provision of CP13 and PHF1 antibodies. We thank the following funding agencies for their support: B.W. received support from the NIH (AG050471, NS089544 and ES020395), BrightFocus Foundation, Alzheimer Association, Cure Alzheimer’s Fund and the Thome Medical Foundation; U.D. received support from a UGC-Raman Fellowship and the Government of India; T.I. received support from the NIH (R01 AG054199); H.L. received support from the Paul F. Glenn Foundation. Publisher Copyright: © 2017 The Author(s).

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.

AB - Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.

UR - http://www.scopus.com/inward/record.url?scp=85039154233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039154233&partnerID=8YFLogxK

U2 - 10.1038/s41593-017-0022-z

DO - 10.1038/s41593-017-0022-z

M3 - Article

C2 - 29273772

AN - SCOPUS:85039154233

SN - 1097-6256

VL - 21

SP - 72

EP - 82

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 1

ER -

Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this