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Ever since ALS was fully described by Jean Martin Charcot more than 120 years ago, this disease has been enigmatic. Lou Gehrig, one of the greatest baseball players of all times, was stricken by this mysterious disease, which forced him to retire and killed him in 2 years. Since the 1930s, this disease has become widely known in the United States as "Lou Gehrig's disease." Even to the neurologic community, ALS was felt to be too obscure to investigate aggressively for sometime thereafter. However, this perception has changed gradually throughout the past 2 decades. We have entered into a most exciting time in ALS research. A cause of familial ALS has been discovered, and the first medication for ALS has been approved by the United States Food and Drug Administration. We are beginning to unravel the mystery of this disease.
(Figure 1) lists the current approaches being used in the search for the pathogenesis of ALS. As a result of ALS research, our current knowledge is highlighted by our understanding of the mechanisms of cell death in motor neurons. Glutamate excitotoxicity begins with increased calcium entry into the neuron, but excessive calcium ions are normally …
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