Examining the evidence for apoptosis in ALS

A review examining evidence for the involvement of apoptosisis in amyotrophic lateral sclerosis (ALS) motor neurone degeneration also describes potential therapeutic agents that could modulate the pathway and slow disease progression.Studies in cell models, transgenic mice and human tissue provide what the authors say is "clear evidence that a programmed mechanism of cell death resembling apoptosis is responsible for motor neuron degeneration in amyotrophic lateral sclerosis." Apoptosis involves morphological changes and death of isolated single cells with the absence of inflammatory cells, in contrast to necrosis, which is associated with clusters of cells dying and a marked neutrophilic inflammatory response. The authors say, "Apoptosis, unlike necrosis, is a process that needs energy." They review in vitro and in vivo evidence of morphological changes in motor neurones, activation of caspases, alterations in Bcl-2 oncoproteins, involvement of death receptors and expression of apoptosis-related molecules.Most of the evidence linking ALS to apoptosis comes from studying SOD1 mutations, which the authors acknowledge is only one disease subtype. However, they say the results can be extrapolated to non-SOD1 and sporadic forms of ALS because the similar clinical presentations and pathology of all forms of ALS suggest a common pathological mechanism in the death of motor neurones. The authors explain that the apoptotic cascade is probably only the terminal event in ALS motor neurone injury, and there is concern that inhibition of apoptosis merely preserves the viability of dysfunctional motor neurones. Therefore, a combination of treatments that target different parts of the disease pathway is more likely to be effective. The authors describe the current evidence on minocycline, calcium channel blockers, cyclosporin, and rasagiline in ALS transgenic mice.Reference...