TMEM106B: a strong FTLD disease modifier
نویسندگان
چکیده
منابع مشابه
The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes.
TMEM106B is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology. TMEM106B localizes to lysosomes, but its function remains unclear. We show that TMEM106B knockdown in primary neurons affects lysosomal trafficking and blunts dendritic arborization. We identify microtubule-associated protein 6 (MAP6) as novel interacting protein for TMEM106B. MAP6 over-expression inhib...
متن کاملExpression of TMEM106B, the frontotemporal lobar degeneration-associated protein, in normal and diseased human brain
BACKGROUND Frontotemporal lobar degeneration (FTLD) is the second most common cause of dementia in individuals under 65 years old and manifests as alterations in behavior, personality, or language secondary to degeneration of the frontal and/or temporal lobes. FTLD-TDP, the largest neuropathological subset of FTLD, is characterized by hyperphosphorylated, ubiquitinated TAR DNA-binding protein 4...
متن کاملIncreased Expression of Frontotemporal Dementia Risk Factor Tmem106b Alters Lysosomal and Autophagosomal Pathways
Frontotemporal lobar degeneration (FTLD) is an important cause of dementia in individuals under age 65. Common variants in the TMEM106B gene were previously discovered by genome-wide association (GWAS) to confer genetic risk for FTLD-TDP, the largest neuropathological subset of FTLD (p=1x10-11, OR=1.6). Prior to its discovery in the GWAS, TMEM106B, or Transmembrane Protein 106B, was uncharacter...
متن کاملTMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways.
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a fatal neurodegenerative disease with no available treatments. Mutations in the progranulin gene (GRN) causing impaired production or secretion of progranulin are a common Mendelian cause of FTLD-TDP; additionally, common variants at chromosome 7p21 in the uncharacterized gene TMEM106B were recently linked by genome-wide as...
متن کاملElevated TMEM106B levels exaggerate lipofuscin accumulation and lysosomal dysfunction in aged mice with progranulin deficiency
Mutations resulting in haploinsufficiency of progranulin (PGRN) cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. Accumulating evidence suggest a crucial role of progranulin in maintaining proper lysosomal function during aging. TMEM106B has been identified as a risk factor for frontotemporal lobar degeneration with pr...
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ژورنال
عنوان ژورنال: Acta Neuropathologica
سال: 2014
ISSN: 0001-6322,1432-0533
DOI: 10.1007/s00401-014-1249-3