FIGURE 3.

Local translation defects in ALS/FTD and SMN. (A) Among ALS/FTD-linked proteins, TDP-43, FUS, and C9orf72 are found. The RBPs TDP-43 and FUS play a role in RNA metabolism. The aggregates usually found in ALS and FTD patients impair TDP-43 and FUS function leading to altered mRNA localization and the consequent cytoskeletal deregulation and stress-mediated intra-axonal translation inhibition, respectively. The GGGCC repeat expansion in the C9orf72 mRNA triggers its assembly in RNP granules, which are erroneously localized to neuritic compartments and affect to nerve branching. (B) Loss of SMN is the main cause of SMA. SMN is involved in the localization of mRNAs to the axonal compartment. SMN defects lead to Actb, Nrn1, Gap43, and Anxa2 mislocalization with important impact in neurite growth, presynaptic function, and cytoskeleton plasticity. SMN also controls the regulator of local translation mTOR through miR-183. *PD miRNAs are also involved in the translation repression induced by mutant LRRK2 in PD. Due to local miRNAs have been identified as contributors to other pathologies, a similar local mechanism could participate in the pathogenesis of PD.