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Dysregulated molecular pathways in amyotrophic lateral sclerosis–frontotemporal dementia spectrum disorder
Author(s) -
Gao FenBiao,
Almeida Sandra,
LopezGonzalez Rodrigo
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797568
Subject(s) - c9orf72 , frontotemporal dementia , amyotrophic lateral sclerosis , biology , neuroscience , dementia , rna splicing , trinucleotide repeat expansion , tardbp , frontotemporal lobar degeneration , genetics , disease , gene , medicine , pathology , rna , allele
Frontotemporal dementia ( FTD ), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD overlaps extensively with the motor neuron disease amyotrophic lateral sclerosis ( ALS ), especially at the genetic level. Both FTD and ALS can be caused by many mutations in the same set of genes; the most prevalent of these mutations is a GGGGCC repeat expansion in the first intron of C9 ORF 72 . As shown by recent intensive studies, some key cellular pathways are dysregulated in the ALS ‐ FTD spectrum disorder, including autophagy, nucleocytoplasmic transport, DNA damage repair, pre‐ mRNA splicing, stress granule dynamics, and others. These exciting advances reveal the complexity of the pathogenic mechanisms of FTD and ALS and suggest promising molecular targets for future therapeutic interventions in these devastating disorders.