Figure 2.

Potential mechanisms of neurodegeneration induced by altered miRNA networks. Schematic representation of cellular pathways that could be affected downstream of miRNAs. (1) Defects in miRNAs could increase the levels of aggregation-prone proteins either directly (i.e., miR-106a and APP in AD) or indirectly (i.e., miR-107 acting through BACE1 or miR-137 acting through serine palmitoyltransferase in AD). (2) miRNAs could control the expression of proteins involved in proper folding or quality control, increasing the risk of protein aggregation. (3) miRNAs could impair the removal of aggregated proteins and therefore increase their levels and toxicity. (4) Finally, altered miRNAs might result in neuronal cell death due to increased levels of certain transcription factors (i.e., miR-124 controls neuronal survival by limiting the expression of Lhx2) or the imbalance between pro-survival and pro-apoptotic signals (i.e., in FTD, polymorphism rs5848 results in more efficient binding of miR-659 and decreased levels of the pro-survival factor progranulin).