Survival motor neuron (SMN) protein in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving mainly the upper and lower motor neurons of adult humans. With regard to the pathomechanism of spinal anterior horn cell (AHC) degeneration in ALS, copy number abnormalities of the survival motor neuron (SMN) genes have been reported in sporadic (s) ALS. SMN protein is the protein responsible for the pathogenesis of spinal muscular atrophy (SMA), an autosomal recessive disease characterized by lower motor neuron loss and muscle atrophy. The disease is caused by deficiency of SMN protein induced by mutation of one of the SMA-associated genes, SMN1. To clarify the role of SMN protein in the degeneration of spinal AHCs in sALS, we examined the amount of cytoplasmic SMN protein in individual AHCs using cytofluorophotometry in 9 patients with sALS and 10 control subjects. It was found that: 1) SMN protein was present in the cytoplasm, nucleus and nucleolus of AHCs and in the nucleus of glial cells, 2) expression of SMN protein in AHCs was significantly associated with cell size in both sALS patients and controls, 3) expression of SMN protein per unit area in AHCs was similar in sALS patients and controls. These findings suggest that: 1) the amount of SMN protein in the cytoplasm of AHCs is strictly controlled in accordance with cell size, in both sALS patients and controls, 2) the amount of SMN protein in the AHCs of sALS patients may be reduced when the AHCs are atrophic, and 3) decrease of SMN protein in the AHCs of sALS patients may be a secondary, and not primary, phenomenon according to their sizes.