Mef2d-mef2c pathways are altered in lymphomonocytes of patients with sporadic and familial form of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease characterized by motor neuron loss. MEF2D and MEF2C are members of MEF2 (myocyte enhancer factor 2) family, a group of transcriptional factors playing a crucial role both in muscle than in neural development and maintenance; for this reason a possible their involvement in ALS context has been assessed. A cohort of 30 ALS patients with sporadic form (sALS), 9 familial ALS patients with mutations in SOD1 gene (fALS) and 30 healthy controls was recruited for the study. Gene expression analysis performed in peripheral blood mononuclear cells (PBMC), revealed a strong increased in MEF2D and MEF2C levels both in sporadic and in familial ALS patients. Although protein levels were unchanged, a different pattern of distribution for MEF2D-MEF2C proteins in patient cells was found, suggesting a possible lack of their function. To evaluate the transcriptional activity of these factors mRNA levels of their downstream targets BDNF, KLF6, RUFY3 and NPEPPS were assessed. Our results showed a significant down-regulation of BDNF, KLF6 and RUFY3 levels confirming that transcriptional activity of both MEF2D and MEF2C isoforms was altered in sporadic and familial ALS patients. In conclusion, we observed evidences of a systemic alteration of MEF2D and MEF2C pathways in ALS patients independently from the presence of SOD1 gene mutations, highlighting a possible common feature between the sporadic and the familiar form of disease.