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Age-dependent formation of TMEM106B amyloid filaments in human brains.
Schweighauser, Manuel; Arseni, Diana; Bacioglu, Mehtap; Huang, Melissa; Lövestam, Sofia; Shi, Yang; Yang, Yang; Zhang, Wenjuan; Kotecha, Abhay; Garringer, Holly J; Vidal, Ruben; Hallinan, Grace I; Newell, Kathy L; Tarutani, Airi; Murayama, Shigeo; Miyazaki, Masayuki; Saito, Yuko; Yoshida, Mari; Hasegawa, Kazuko; Lashley, Tammaryn; Revesz, Tamas; Kovacs, Gabor G; van Swieten, John; Takao, Masaki; Hasegawa, Masato; Ghetti, Bernardino; Spillantini, Maria Grazia; Ryskeldi-Falcon, Benjamin; Murzin, Alexey G; Goedert, Michel; Scheres, Sjors H W.
Afiliação
  • Schweighauser M; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Arseni D; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Bacioglu M; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Huang M; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Lövestam S; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Shi Y; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Yang Y; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Zhang W; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
  • Kotecha A; Medical Research Council Prion Unit, Institute of Prion Diseases, University College London, London, UK.
  • Garringer HJ; Thermo Fisher Scientific, Eindhoven, The Netherlands.
  • Vidal R; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Hallinan GI; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Newell KL; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Tarutani A; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Murayama S; Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
  • Miyazaki M; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, University of Osaka, Osaka, Japan.
  • Saito Y; Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Yoshida M; Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
  • Hasegawa K; Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
  • Lashley T; Division of Neurology, Sagamihara National Hospital, Sagamihara, Japan.
  • Revesz T; Department of Neurodegenerative Disease and Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.
  • Kovacs GG; Department of Neurodegenerative Disease and Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.
  • van Swieten J; Tanz Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Takao M; Institute of Neurology, Medical University of Vienna, Vienna, Austria.
  • Hasegawa M; Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands.
  • Ghetti B; Department of Clinical Laboratory, National Center of Neurology and Psychiatry, National Center Hospital, Tokyo, Japan.
  • Spillantini MG; Department of Neurology, Mihara Memorial Hospital, Isesaki, Japan.
  • Ryskeldi-Falcon B; Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
  • Murzin AG; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Goedert M; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Scheres SHW; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Nature ; 605(7909): 310-314, 2022 05.
Article em En | MEDLINE | ID: mdl-35344985
Many age-dependent neurodegenerative diseases, such as Alzheimer's and Parkinson's, are characterized by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-ß, α-synuclein and transactive response DNA-binding protein (TARDBP; also known as TDP-43) are the most common1,2. Here we used structure determination by cryogenic electron microscopy to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including those resulting from sporadic and inherited tauopathies, amyloid-ß amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 individuals with normal neurology and no or only a few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29-kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific to the carboxy-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, individuals with normal neurology indicates that they form in an age-dependent manner.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Envelhecimento / Amiloide / Amiloidose / Proteínas de Membrana / Proteínas do Tecido Nervoso Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Envelhecimento / Amiloide / Amiloidose / Proteínas de Membrana / Proteínas do Tecido Nervoso Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2022 Tipo de documento: Article