**10. Other dysregulate miR**

De Felice et al. [51] analyzed 911 mRNA expression by microarray in leukocytes of 14 patients with sporadic ALS. In addition to miR-338-3p, they identified eight miRNAs with changes in expression, e.g., hsa-miR-451, hsa-miR-1275, hsa-miR-328, hsamiR-638, has-miR-149, and the expression decreased for miR583 and miR-665 [51]. Campos-Melo et al. [79] also reported a decrease in most miRNAs, such as miR-146a, miR-524-5, and miR-582-3, from neurons of the spinal cord in the lower back. In addition, miR-b2403 and miR-b1336 are underregulated in the spinal cord samples; both are related to the stabilization of mRNA NEFL as well as miR-338-3 as previously reported [50, 51]. The consequence of the accumulation effects on the NEFL mRNA could be the cause for the decrease in mRNA previously reported in patients with spinal cord ELA [47]. Reports of miRNAs expression analysis performed on the samples of neurons recovered from the brain or spinal cord of ALS patients have been able to confirm a reduction in miRNAs that modulate gene NEFL stability (for the synthesis of light neurofi‐ lament), the cytochrome *c* oxidase gene, and protein of the nuclear membrane NAV3 and related neuronal regeneration.

Other cells that contribute to the disease are microglia cells, lymphocytes, and Schwann cells [89–91]. A recent hypothesis is that Schwann and muscle cells are also direct partners of the injured motor axons and may respectively be the recipients or initiators of the initial damage [67, 92].

In a mice ALS model, it has been proved that miR-365 and miR-125b suppress the IL-6/STAT3 pathway in microglia cells with an increase in the levels of TNFα mRNA [93]. This agrees with the fact that TNFα is upregulated in G93A mice and ALS patients [94, 95], which indicates that miR-365 and miR-125b dysregulations might develop the pathological cytokine profile on ALS.
