Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.

Autor:	Chang A; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Xiang X; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA., Wang J; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Lee C; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA; Department of Microbiology & Immunology, Columbia University, New York, NY 10032, USA., Arakhamia T; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Simjanoska M; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Wang C; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA., Carlomagno Y; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Zhang G; Proteomics and Metabolomics Core Facility, Weill Cornell Medicine, New York, NY 10021, USA., Dhingra S; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA., Thierry M; Centre for Cognitive Neurology, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA., Perneel J; Applied and Translational Neurogenomics, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Heeman B; Applied and Translational Neurogenomics, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Forgrave LM; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, Vancouver, Canada., DeTure M; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., DeMarco ML; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, Vancouver, Canada., Cook CN; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Rademakers R; Applied and Translational Neurogenomics, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Petrucelli L; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Stowell MHB; Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: stowellm@colorado.edu., Mackenzie IRA; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada. Electronic address: ian.mackenzie@vch.ca., Fitzpatrick AWP; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA. Electronic address: anthony.fitzpatrick@columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2022 Apr 14; Vol. 185 (8), pp. 1346-1355.e15. Date of Electronic Publication: 2022 Mar 04.
DOI:	10.1016/j.cell.2022.02.026
Abstrakt:	Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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