Targeting LINE‑1 Retrotransposon Activity to Address Neurodegeneration & Inflammation in ALS

  • LINE‑1 retrotransposons can become aberrantly active under stress, contributing to genomic instability and neuroinflammation in ALS
  • Selective LINE‑1 reverse transcriptase inhibitors suppress cytosolic LINE‑1 activity and blunt innate immune activation
  • Preclinical models show neuroprotective effects, supporting motor neuron survival and reducing pathological signaling
  • Translational considerations include biomarker development, CNS delivery, and differentiating selective inhibitors from earlier non‑specific approaches