Mechanisms of cell death and treatment prospects in motor neuron disease

PJ Shaw
Department of Neurology, University of Sheffield and Royal Hallamshire Hospital, Beech Hill Road, Sheffield, United Kingdom

Scientific evidence is emerging to indicate that motor neuron injury in motor neuron disease may reflect a complex interplay between genetic factors, oxidative stress, and imbalance of the glutamatergic excitatory control of motor neurons, which may result in damage to critical target proteins and organelles. The relative importance of these factors is likely to vary in different subgroups of patients. Protein aggregation may play a role in some forms of motor neuron injury, and the eventual demise of motor neurons may occur by a programmed cell death pathway. Advances in symptomatic therapy for patients with motor neuron disease include the development of specialist clinics, with input from multidisciplinary teams, as well as hospice care in the late stages of the disease. A number of recent therapeutic trials of potential neuroprotective drugs have been conducted, including antiglutamate, antioxidant, and neurotrophic agents. To date, only the antiglutamate agent riluzole has been shown to reproducibly prolong the survival of patients with motor neuron disease. Future therapy in motor neuron disease is likely to include a ÔcocktailÕ of neuroprotective compounds to interfere with several molecular pathway that lead to neuronal injury. In using therapeutic strategies aimed towards retarding or arresting motor neuron disease, close attention will need to be paid to quality of life issues.

Hong Kong Med J 2001;7:267-80

Key words: Apoptosis; Mitochondrial dysfunction; Motor neuron disease; Neuroprotein; Oxidative stress