title: [Clinical and pathological spectrum of TDP-43 associated ALS].
abstract: The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 KDa (TDP-43) immunopositive cytoplasmic inclusions have been found in glia and neurons of ALS patients. The discovery of TDP-43 mutations in ALS patients indicates a direct role of TDP-43 in ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP-43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore, the neuropathological findings for ALS-10, including TDP-43 immunopositive inclusions and Bunina bodies, are identical to those in sporadic ALS. Most of the mutations are located in the C-terminus of TDP-43, which may function as a binding domain of heterogeneous nuclear ribonucleoprotein. Frontotemporal lobar degeneration: FTLD and FTLD/MND (motor neuron disease) also have TDP-43 immunopositive inclusions. These disorders have been named as TDP-43 proteinopathy. However, patients with TDP-43 mutations rarely develop FTLD. Causative genes for familial FTLD and FTLD/MND are not linked to the TDP-43 gene. Thus, other factors may contribute to the TDP-43 pathology in these diseases. Further analysis is required to elucidate the molecular mechanism of ALS-10 and TDP-43 proteinopathy.
authors.affiliation: Department of Molecular Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, Niigata University.
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.forename: Akio
authors.initials: A
authors.lastname: Yokoseki
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Tan
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ishihara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nishiira
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D057174:Frontotemporal Lobar Degeneration; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D057177:TDP-43 Proteinopathies
chemical_list: D004268:DNA-Binding Proteins