@article{b5fc0af386544d95a9d1b4d6fc4be878,
title = "Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue",
abstract = "The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.",
author = "Dhavale, {Dhruva D.} and Barclay, {Alexander M.} and Borcik, {Collin G.} and Katherine Basore and Berthold, {Deborah A.} and Gordon, {Isabelle R.} and Jialu Liu and Milchberg, {Moses H.} and O{\textquoteright}Shea, {Jennifer Y.} and Rau, {Michael J.} and Zachary Smith and Soumyo Sen and Brock Summers and John Smith and Warmuth, {Owen A.} and Perrin, {Richard J.} and Perlmutter, {Joel S.} and Qian Chen and Fitzpatrick, {James A.J.} and Schwieters, {Charles D.} and Emad Tajkhorshid and Rienstra, {Chad M.} and Kotzbauer, {Paul T.}",
note = "Support for this work was provided by: grants from the Michael J. Fox Foundation; NIH grants NS110436, NS097799, and NS075321 from the National Institute of Neurological Disorders and Stroke and National Institute on Aging; P41GM136463 from the National Institute of General Medical Sciences; the American Parkinson Disease Association (APDA) Advanced Research Center for Parkinson Disease at Washington University in St. Louis; the Greater St Louis Chapter of the APDA. We are grateful for the technical support of the Betty Martz Laboratory for Neurodegenerative Research at Washington University in St. Louis (PK). We acknowledge the assistance of Dr. Rocio Bengoechea with the immunoblots. CS was supported by the Intramural Research Programs of NIDDK and NHLBI at the National Institutes of Health. OW was supported by the Molecular Biophysics Predoctoral Training Grant T32GM130550 from NIGMS. CB is supported by the NIH Ruth L. Kirschstein Fellowship (F32-GM149118) from NIGMS. Figure created with Biorender.com. Support for this work was provided by: grants from the Michael J. Fox Foundation; NIH grants NS110436, NS097799, and NS075321 from the National Institute of Neurological Disorders and Stroke and National Institute on Aging; P41GM136463 from the National Institute of General Medical Sciences; the American Parkinson Disease Association (APDA) Advanced Research Center for Parkinson Disease at Washington University in St. Louis; the Greater St Louis Chapter of the APDA. We are grateful for the technical support of the Betty Martz Laboratory for Neurodegenerative Research at Washington University in St. Louis (PK). We acknowledge the assistance of Dr. Rocio Bengoechea with the immunoblots. CS was supported by the Intramural Research Programs of NIDDK and NHLBI at the National Institutes of Health. OW was supported by the Molecular Biophysics Predoctoral Training Grant T32GM130550 from NIGMS. CB is supported by the NIH Ruth L. Kirschstein Fellowship (F32-GM149118) from NIGMS. Figure 1a created with Biorender.com.",
year = "2024",
month = dec,
doi = "10.1038/s41467-024-46832-5",
language = "English (US)",
volume = "15",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}