A mechanistic model of tau amyloid aggregation based on direct observation of oligomers

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. / Shammas, Sarah L; Garcia, Gonzalo A; Kumar, Satish; Kjaergaard, Magnus; Horrocks, Mathew H; Shivji, Nadia; Mandelkow, Eva; Knowles, Tuomas P J; Mandelkow, Eckhard; Klenerman, David.

I: Nature Communications, Bind 6, 2015, s. 7025.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Shammas, SL, Garcia, GA, Kumar, S, Kjaergaard, M, Horrocks, MH, Shivji, N, Mandelkow, E, Knowles, TPJ, Mandelkow, E & Klenerman, D 2015, 'A mechanistic model of tau amyloid aggregation based on direct observation of oligomers', Nature Communications, bind 6, s. 7025. https://doi.org/10.1038/ncomms8025

APA

Shammas, S. L., Garcia, G. A., Kumar, S., Kjaergaard, M., Horrocks, M. H., Shivji, N., Mandelkow, E., Knowles, T. P. J., Mandelkow, E., & Klenerman, D. (2015). A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. Nature Communications, 6, 7025. https://doi.org/10.1038/ncomms8025

CBE

Shammas SL, Garcia GA, Kumar S, Kjaergaard M, Horrocks MH, Shivji N, Mandelkow E, Knowles TPJ, Mandelkow E, Klenerman D. 2015. A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. Nature Communications. 6:7025. https://doi.org/10.1038/ncomms8025

MLA

Vancouver

Shammas SL, Garcia GA, Kumar S, Kjaergaard M, Horrocks MH, Shivji N o.a. A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. Nature Communications. 2015;6:7025. https://doi.org/10.1038/ncomms8025

Author

Shammas, Sarah L ; Garcia, Gonzalo A ; Kumar, Satish ; Kjaergaard, Magnus ; Horrocks, Mathew H ; Shivji, Nadia ; Mandelkow, Eva ; Knowles, Tuomas P J ; Mandelkow, Eckhard ; Klenerman, David. / A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. I: Nature Communications. 2015 ; Bind 6. s. 7025.

Bibtex

@article{a9d40e8126254757a2e1531307391dd1,
title = "A mechanistic model of tau amyloid aggregation based on direct observation of oligomers",
abstract = "Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.",
author = "Shammas, {Sarah L} and Garcia, {Gonzalo A} and Satish Kumar and Magnus Kjaergaard and Horrocks, {Mathew H} and Nadia Shivji and Eva Mandelkow and Knowles, {Tuomas P J} and Eckhard Mandelkow and David Klenerman",
year = "2015",
doi = "10.1038/ncomms8025",
language = "English",
volume = "6",
pages = "7025",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - A mechanistic model of tau amyloid aggregation based on direct observation of oligomers

AU - Shammas, Sarah L

AU - Garcia, Gonzalo A

AU - Kumar, Satish

AU - Kjaergaard, Magnus

AU - Horrocks, Mathew H

AU - Shivji, Nadia

AU - Mandelkow, Eva

AU - Knowles, Tuomas P J

AU - Mandelkow, Eckhard

AU - Klenerman, David

PY - 2015

Y1 - 2015

N2 - Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.

AB - Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.

U2 - 10.1038/ncomms8025

DO - 10.1038/ncomms8025

M3 - Journal article

C2 - 25926130

VL - 6

SP - 7025

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -