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Results: 3

1.
Figure 3

Figure 3. From: Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration.

Potential mechanisms of miRNA deregulation downstream of protein aggregation/dysfunction. Two basic mechanisms could affect miRNA regulatory networks: (1) alteration of miRNA levels through deregulation of transcription (i.e., miR-9 downstream of HTT and REST) or processing (i.e., TDP-43 altering Drosha function) and (2) interference with RISC activity (i.e., ataxin-2 seems to be required for optimal miRNA silencing).

Eduardo Gascon, et al. Front Neurosci. 2012;6:48.
2.
Figure 1

Figure 1. From: Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration.

The canonical miRNA biogenesis pathway. miRNAs are produced from long Pol II transcripts (pri-miRNA). A nuclear complex containing Drosha (purple oval) and DGCR8 (pink oval) cleaves the primary transcript and generates a precursor miRNA (pre-miRNA). After nuclear export, pre-miRNA is further processed by Dicer (blue croissant). Then, Ago2 (yellow oval) binds to the complex formed by miRNA duplex and Dicer. Ago2 induces Dicer dissociation and the release of the passenger strand from the complex. Finally, other proteins, such as GW182 (dark blue), associate with Ago2 and form a RISC complex that recognizes and then silences (by mRNA degradation and/or translation inhibition) a target mRNA.

Eduardo Gascon, et al. Front Neurosci. 2012;6:48.
3.
Figure 2

Figure 2. From: Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration.

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).

Eduardo Gascon, et al. Front Neurosci. 2012;6:48.

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