| First Author | Duarte-Ruiz M | Year | 2025 |
| Journal | Cell Death Dis | Volume | 17 |
| Issue | 1 | Pages | 73 |
| PubMed ID | 41360765 | Mgi Jnum | J:378358 |
| Mgi Id | MGI:8281052 | Doi | 10.1038/s41419-025-08301-9 |
| Citation | Duarte-Ruiz M, et al. (2025) Regulation of NTRK2 alternative splicing by PRPF40B controls neural differentiation and synaptic plasticity. Cell Death Dis 17(1):73 |
| abstractText | BDNF signaling through its receptor TRKB plays a critical role in brain development, neuroplasticity, and homeostasis. Alternative splicing of the TRKB gene, NTRK2, generates either the full-length receptor (TRKB-FL) or a truncated isoform (TRKB-T1) that inhibits BDNF signaling and has been implicated in neurodegenerative diseases, psychiatric disorders, and cognitive impairments. Here, we show that PRPF40B, a splicing factor associated with neuronal dysfunction, promotes the production of the TRKB-FL isoform during neuronal differentiation. Silencing PRPF40B increases TRKB-T1 expression and impairs the expression of genes important for neuronal differentiation and synaptic plasticity, both in vitro and in vivo, during early embryogenesis. Our data thus identify PRPF40B as a key regulator of the balance between TRKB receptor isoforms, crucial for fine-tuning neuronal responses and for preventing neuroplasticity or survival impairments, providing also a mechanism for the role of PRPF40B in the pathogenesis of various human neurodegenerative diseases and psychiatric disorders. |
