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Background  Amyotrophic lateral sclerosis is a chronic neurodegenerative disease characterized by progressive paralysis due to degeneration of motor neurons by unknown causes. Recent evidence shows that Wnt signaling is involved in neurodegenerative processes, including Amyotrophic Lateral Sclerosis. However, to date, little is known regarding the expression of Wnt signaling components in this fatal condition. In the present study we used transgenic SOD1 G93A  mice to evaluate the expression of several Wnt signaling components, with special focus on Frizzled-5 cellular expression alteration along disease progression.    Findings  Based on previous studies demonstrating the expression of Wnts and their transcriptional regulation during Amyotrophic lateral sclerosis development, we have analyzed the mRNA expression of several Wnt signaling components in the spinal cord of SOD1 G93A  transgenic mice at different stages of the disease by using real time quantitative PCR analysis. Strikingly, one of the molecules that seemed not to be altered at mRNA level, Frizzled-5, showed a clear up-regulation at late stages in neurons, as evidenced by immunofluorescence assays. Moreover, increased Frizzled-5 appears to correlate with a decrease in NeuN signal in these cells, suggesting a correlation between neuronal affectation and the increased expression of this receptor.    Conclusions  Our data suggest the involvement of Wnt signaling pathways in the pathophysiology of Amyotrophic Lateral Sclerosis and, more specifically, the implication of Frizzled-5 receptor in the response of neuronal cells against neurodegeneration. Nevertheless, further experimental studies are needed to shed light on the specific role of Frizzled-5 and the emerging but increasing Wnt family of proteins research field as a potential target for this neuropathology.

Wnt Signaling Alteration in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Mice: Special Focus on Frizzled-5 Cellular Expression Pattern