Implications of altered brain ganglioside profiles in amyotrophic lateral sclerosis (ALS).

Rapport et al. (11) reported that marked aberrations in brain ganglioside profiles were present in 17 of 21 patients with ALS. The aberrations were detected both in motor cortex and in unexpected regions such as frontal, temporal, and parahippocampal gyrus cortex. These results suggest that some underlying pathological process in ALS also occurs in some neurons that are less vulnerable than motor neurons to consequent deterioration. Since gangliosides are major membrane constituents whose carbohydrate residues establish structural configurations on the external face of the cell membrane, it is highly probable that aberrant ganglioside patterns reflect alterations in receptor structure and function. Receptors are inherently cell specific and the specificity would account for differences in response of sensory and motor neurons to the pathological process in ALS. An apparent absence of similar ganglioside aberrations in spinal cord suggests that the primary pathology is in the brain. Such aberrations are not seen in Alzheimer's disease. If receptor functions are altered in ALS, what ligands might be involved? A major consideration is neurotrophic hormones (2). Gangliosides are known to modulate the effect of nerve growth factor in some in vitro systems and very recent evidence implicates protein kinase activation as an important mechanism.