ABSTRACT
Programmed cell death, or apoptosis, is a highly regulated form of cell death in which cells the by activating a pre-programed suicide mechanism. Early skepticism stemmed from the difficulties in finding clear morphologic evidence of apoptosis in postmortem tissues of Amyotrophic Lateral Sclerosis (ALS) patients. An increasing number of reports show evidence for apoptosis in patients with ALS. Studies of the signal transduction pathways related to apoptosis have also been informative in ALS cases. Limited biochemical evidence has been collected so far in human samples. Apoptosis occurs through activation of two major pathways: the intracellular or the extracellular pathway. Therapeutic manipulation of apoptosis may represent only one way to treat ALS. ALS pathogenesis involves activation of different pathways of cell death that include oxidative stress, deposition of abnormal proteins, axonal strangulation due to neurofilament misaccumulation, excitotoxicty and mitochondrial dysfunction.
