Age-dependent formation of TMEM106B amyloid filaments in human brains.
Nature
; 605(7909): 310-314, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-35344985
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encéfalo
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Envejecimiento
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Amiloide
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Amiloidosis
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Proteínas de la Membrana
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Proteínas del Tejido Nervioso
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido