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Brain Res. 2016 Sep 1;1646:132-138. doi: 10.1016/j.brainres.2016.05.051. Epub 2016 May 30.

14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis.

Author information

1
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.
2
Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-9 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
3
Department of Pathology, Tokyo Women's Medical University, 8-1 Kawatacho, Tokyo 161-0054, Japan.
4
Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.

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.

KEYWORDS:

14-3-3 proteins; Amyotrophic lateral sclerosis; Anterior horn cells; Eta isoform; SNAP25; TDP-43

PMID:
27256400
DOI:
10.1016/j.brainres.2016.05.051
[Indexed for MEDLINE]

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