Publications by authors named "M Lafarga"
Article Synopsis
- Spinal muscular atrophy (SMA) is caused by a lack of survival motor neuron (SMN) protein, leading to the degeneration of lower motor neurons and muscle atrophy.
- Early research in SMNΔ7 mice showed signs of motor dysfunction and myofiber changes before muscle denervation occurred, highlighting that SMN deficiency has direct effects on muscle cells.
- The study revealed ultrastructural abnormalities in muscle fibers, including disruptions in the myofibrillar structure and altered mitochondrial dynamics, suggesting that muscle changes occur independently of motor neuron loss in SMA.
Article Synopsis
- * Previous research found that increasing miR-30c levels can worsen neuropathic pain, while reducing it can prevent pain onset and reverse allodynia.
- * This study focused on the role of miR-30c-5p, revealing that it worsens neuron damage and stress in the DRG after nerve injury, suggesting that targeting miR-30c-5p could offer a new way to treat neuropathic pain.
SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells.
View Article and Find Full Text PDFObjective: Genome wide association studies have identified an exon 6 deletion variant that associates with increased risk of pancreatic cancer. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in , the mouse orthologue of .
Design: We used CRISPR/Cas9 to introduce a 707bp deletion in encompassing exon 6 ( ).
The escape of mitochondrial double-stranded dsRNA (mt-dsRNA) into the cytosol has been recently linked to a number of inflammatory diseases. Here, we report that the release of mt-dsRNA into the cytosol is a general feature of senescent cells and a critical driver of their inflammatory secretome, known as senescence-associated secretory phenotype (SASP). Inhibition of the mitochondrial RNA polymerase, the dsRNA sensors RIGI and MDA5, or the master inflammatory signaling protein MAVS, all result in reduced expression of the SASP, while broadly preserving other hallmarks of senescence.
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