Abstract
There are four main hypotheses about the cause of ALS: excitotoxicity linked to glutamate receptor overactivation; mutation of the superoxide dismutase gene; production of autoantibodies to calcium channels; neurofilament accumulation. The motoneuron degeneration characteristic of ALS could be caused by any one or a combination of these mechanisms. Future therapeutic approaches should be based on these mechanisms and given in combination so that different levels of the degenerative process are targeted. Protection against excitotoxicity could be achieved with a combination of pharmacologic agents having neuroprotective activity, such as antiglutamate agents (e.g., riluzole), N-methyl-D-aspartate (NMDA) and non-NMDA antagonists, free-radical scavengers, calcium-channel blockers, and neurotrophic factors. Gene transfer is a possible future approach when causative mutations are identified. Transfer of genes encoding neuroprotective agents or genetically modified cells stably expressing these agents is another possible strategy.
Citations
Mar 11, 1999·Archives of Pharmacal Research·H J Kim, J S Kwon
Nov 9, 2000·European Journal of Pharmacology·G De SarroA De Sarro
Jun 27, 2003·European Journal of Pharmacology·Ajit G ThomasBarbara S Slusher
Jan 12, 2002·Brain Research Bulletin·A E WillingP R Sanberg
Jul 25, 2000·British Journal of Pharmacology·T JehleT J Feuerstein
Jun 20, 1998·Neuropathology and Applied Neurobiology·E M Fisher
Apr 2, 2002·Experimental Neurology·Svitlana Garbuzova-DavisPaul R Sanberg
Mar 6, 2007·Neurobiology of Disease·Carmen CabanesSalvador Martínez
Oct 18, 2002·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Garth L NicolsonJohn Pomfret
Dec 11, 1999·Journal of Child Neurology·J B Strober, G I Tennekoon
Feb 9, 2002·Synapse·Cristina ZonaGiorgio Bernardi
Mar 16, 2012·The Cochrane Database of Systematic Reviews·Robert G MillerDan H Moore
Aug 24, 1999·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J Finsterer, B Mamoli
Jul 3, 1999·Physiological Reviews·A MeirR Rahamimoff
Oct 28, 1998·Physiological Reviews·M R Picciotto, K Wickman
May 18, 1999·Biophysical Chemistry·T WeiA Mori