A neurotoxic cryptic peptide arising from TDP-43-dependent cryptic splicing of PKN1 - PubMed
2 days ago
- #cryptic splicing
- #TDP-43
- #neurodegeneration
- A neurotoxic cryptic peptide, PKN1-N207 (PKN207), arises from TDP-43-dependent cryptic splicing of PKN1.
- TDP-43 dysfunction in ALS and AD leads to aberrant RNA splicing, producing stable pathogenic proteins.
- PKN1-5a1, a TDP-43-repressed cryptic exon in PKN1, is activated in ALS patient brains and introduces a premature termination codon.
- The aberrant transcript escapes nonsense-mediated decay and is translated into PKN207, detectable in AD brains with TDP-43 pathology.
- In mice, PKN207 impairs cognition, memory, and synaptic plasticity.
- The study reveals a peptide-mediated mechanism in TDP-43 proteinopathies.