**6. Conclusions**

There is no doubt that TNF- play key roles in degenerative conditions afflicting CNS, also in ALS. The precise role TNF- plays remain highly controversial due to the complexity and pleiotropic nature of this cytokine and its activities during critical developmental and homeostatic cellular processes. Multiple factors determine whether TNF- will exert deleterious or beneficial effects for neuronal survival and some of these differential actions relate to its duration of expression, concentration, receptor conformation. Despite the elaborate and promising data collected thus far to assign function to TNF- in neurodegeneration, surprisingly little is still known about the cellular and stage-specific roles of this cytokine.

The data reported in this chapter also underline the importance of TNF- pathways in ALS pathology due to the interaction with SOD1 gene.

In fact, the data that demonstrated the down-regulation of SOD1 after treatment with TNF- (Afonso et al., 2006), related to the up-regulation of SOD1 mRNA expression in ALS patients suggest to carry on the studies about TNF- in ALS disease to better define the TNF function in neurodegeneration. A better understanding of SOD1 regulation related to TNF function may permit to develop novel immunotherapy application in ALS disease.
