Excitotoxicity, Genetics and Neurodegeneration in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is one of the commonest human neurodegenerative disorders of adult life. The cell-death process in ALS is relatively selective for upper motor neurones, a proportion of which are represented by Betz cells (Fig. lA) in the fifth layer of the motor cortex, and for lower motor neurones in the ventral horn of the spinal cord (Fig. 1B) and brainstem. The selective vulnerability of motor neurones in ALS is relative and, there is now increasing evidence from pathological (Ince et al. 1996; Iwanaga et al. 1997; Williams et al. 1995) and clinical (Chari et al. 1996; Kew et al. 1993; Subramaniam and Yiannikas 1990) studies that extra-motor system involvement commonly occurs, and that ALS is in fact a multisystem disorder. As a result of the neurodegenerative process, the individual afflicted by ALS develops progressive muscle weakness, wasting and spasticity and usually dies from respiratory failure within 3–5 years from the onset of symptoms. One of the interesting clinical features in ALS is that certain groups of motor neurones tend to be selectively spared from injury, including those brainstem nuclei innervating extraocular muscles responsible for eye movement and those in Onuf’s nucleus in the sacral spine cord innervating the muscles of the pelvic floor.