title: 14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis.
abstract: The immunolocalization of the 14-3-3 eta isoform in the anterior horn cells (AHCs) of patients with sporadic amyotrophic lateral sclerosis (ALS) and controls was examined. Compared with the immunolocalization of other 14-3-3 isoforms, the immunolocalization of the 14-3-3 eta isoform was either synaptic at the periphery of AHCs, spindle-shaped in neurites, or granular in the cytoplasm. By double labeling with phosphorylated (p-)TDP-43, the transactivation response DNA binding protein of 43kDa (TDP-43) demonstrated frequent colocalization of the 14-3-3 eta isoform in granular structures (90%) and spindle-shaped structures (85.4%), but not in p-TDP-43-positive round inclusions. It is speculated that the 14-3-3 eta isoform is associated with not only a synaptic pathology of ALS but also TDP-positive small lesions in the cytoplasm and neurites. The absence of eta-like immunoreactivity in p-TDP-43-positive large inclusions suggests the restricted relevance of the 14-3-3 eta isoform during ALS pathogenesis to some phases of the p-TDP pathology.
authors.affiliation: Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-9 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: takahiko@tokyo-med.ac.jp.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Umahara
authors.affiliation: Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-9 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, 8-1 Kawatacho, Tokyo 161-0054, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-9 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanyu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000870:Anterior Horn Cells / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; C000598624:TARDBP protein, human; C482984:YWHAH protein, human
keywords: 14-3-3 proteins; Amyotrophic lateral sclerosis; Anterior horn cells; Eta isoform; SNAP25; TDP-43