Your browser doesn't support javascript.
loading
Loss of TMEM106B exacerbates Tau pathology and neurodegeneration in PS19 mice.
Feng, Tuancheng; Du, Huan; Yang, Cha; Wang, Ya; Hu, Fenghua.
Afiliación
  • Feng T; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
  • Du H; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
  • Yang C; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
  • Wang Y; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
  • Hu F; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA. fh87@cornell.edu.
Acta Neuropathol ; 147(1): 62, 2024 03 25.
Article en En | MEDLINE | ID: mdl-38526799
ABSTRACT
TMEM106B, a gene encoding a lysosome membrane protein, is tightly associated with brain aging, hypomyelinating leukodystrophy, and multiple neurodegenerative diseases, including frontotemporal lobar degeneration with TDP-43 aggregates (FTLD-TDP). Recently, TMEM106B polymorphisms have been associated with tauopathy in chronic traumatic encephalopathy (CTE) and FTLD-TDP patients. However, how TMEM106B influences Tau pathology and its associated neurodegeneration, is unclear. Here we show that loss of TMEM106B enhances the accumulation of pathological Tau, especially in the neuronal soma in the hippocampus, resulting in severe neuronal loss in the PS19 Tau transgenic mice. Moreover, Tmem106b-/- PS19 mice develop significantly increased abnormalities in the neuronal cytoskeleton, autophagy-lysosome activities, as well as glial activation, compared with PS19 and Tmem106b-/- mice. Together, our findings demonstrate that loss of TMEM106B drastically exacerbates Tau pathology and its associated disease phenotypes, and provide new insights into the roles of TMEM106B in neurodegenerative diseases.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Degeneración Lobar Frontotemporal / Demencia Frontotemporal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Degeneración Lobar Frontotemporal / Demencia Frontotemporal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania