14-3-3 proteins in Lewy body-like hyaline inclusions in a patient with familial amyotrophic lateral sclerosis with a two-base pair deletion in the Cu/Zn superoxide dismutase (SOD1) gene

Abstract

14-3-3 proteins are molecular chaperones that regulate various types of signal transduction pathways through phosphorylation-dependent protein-protein interactions [1]. Recently, we demonstrated the immunohistochemical localization of 14-3-3 proteins in Lewy body-like hyaline inclusions (LBHIs) in patients with sporadic amyotrophic lateral sclerosis (SALS) [6]. In the present study, we performed immunohistochemical studies on 14-3-3 proteins in formalin-fixed, paraffin-embedded sections from a patient with familial ALS (FALS), with a two-base pair deletion in the Cu/Zn superoxide dismutase (SOD1) gene, using anti-peptide antibodies that were already confirmed to be specific for human 143-3 proteins [4, 5]. The clinicopathological background of this case has been previously reported [2]. Briefly, this patient was a Japanese woman whose initial symptom was muscle wasting in the right lower limb at the age of 42 years. Her muscle atrophy and weakness spread to all extremities, and she died of respiratory failure about 2 years after the initial onset. She had a family history of a similar neurological disease affecting her older brother, father, and paternal uncle. The histological examination of this case revealed degeneration of the corticospinal tracts (Fig. 1A) as well as severe neuronal loss and reactive astrocytosis in the anterior horn (Fig. 1B). In addition, LBHIs were observed in some motor neurons in the anterior horn (Fig. 1D). The 14-3-3-immunoreactive products were distributed throughout the cell bodies and proximal processes of the remaining anterior horn cells (Fig. 1C). When compared with control cases [6], 14-3-3 immunoreactivity was well preserved in the surviving motor neurons, and these neuronal immunolabeling profiles were similar to those in other areas of the central nervous system, including the oculomotor and Onufrowicz nuclei. Our observations suggest that the levels of 14-3-3 proteins may not be reduced even in anterior horn cells severely affected by FALS. LBHIs in the remaining motor neurons were in