Possible neuroprotective strategies in ALS

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder of unknown aetiology. Progressive motor weakness and bulbar dysfunction lead to premature death, usually from respiratory failure. To date, riluzole is the only disease-modifying drug approved for the treatment of ALS, but this has only a minor impact on the clinical outcome. The clinical development of new drugs for ALS is entirely dependent on the understanding of the aetiology and pathophysiology of the disease, which is still far from being fully elucidated. ALS is a multisystem disorder and can be viewed as the consequence of a complex neurodegenerative process involving neuron-glia interactions. Excitotoxicity, oxidative stress, mitochondrial dysfunction, cytoskeletal defects and apoptosis are all putative mechanisms which seem to operate in ALS and might be amenable of pharmacological intervention. Since the pathogenesis of ALS seems to involve multiple factors, future treatments may target different molecular pathways by a combined multi-drug therapy. © 2004 Bentham Science Publishers Ltd.