Motor Neuron Disease/Amyotrophic Lateral Sclerosis — Lessons from Ubiquitin

Abstract

Ubiquitin is a stress protein implicated in the degradation of short-lived and abnormal proteins. In a neuropathological study of 43 cases with motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and 44 control cases the distribution and specificity of Bunina bodies and ubiquitin-reactive inclusions (UBRI) were investigated. The primary motor area showed nerve cell loss in 67%, Bunina bodies in Betz cells (10%) and UBRI in small pyramidal cells (17%). Degeneration of anterior horn cells in all cases coincided with Bunina bodies (84%) and UBRI (98%) in the same location; the motor nuclei of the caudal brain stem were also involved almost to the same degree. More resistant nuclei like the oculomotor nuclei or the Onuf's nucleus showed no degeneration but UBRI in 11% and 18% of cases, respectively. Like the degenerative process, the formation of UBRI was not confined to motor nuclei but also involved the brain stem reticular formation, substantia nigra, and Clarke's nucleus showing that MND/ALS is a multiple system degeneration. UBRI were found in only one control case in the anterior horn cells and in one case in the hypoglossal nucleus showing that UBRI, although not being absolutely specific for MND/ALS, have practical value for the neuropathological diagnosis of that disease. The pathogenetical implications of UBRI in MND/ALS are discussed.