Overview
- Genome Research published the open-access study online Aug 19–20, detailing LCM-seq and single-molecule FISH across four motor neuron populations in SOD1G93A mice.
- Ocular motor neurons altered few transcripts during disease and instead showed high baseline expression of En1, Pvalb, Cd63, and Gal associated with resistance.
- Vulnerable neurons mounted mixed responses, activating pro-apoptotic pathways (Atf4, Nupr1, Ddit3, Penk) alongside pro-regenerative genes (Atf3, Sprr1a, Vgf, Ina, Fgf21, Gap43, Adcyap1, Mt1) that ultimately failed to prevent degeneration.
- A meta-analysis across four rodent Sod1 datasets defined a shared vulnerability code of 39 genes that captures mechanisms common to susceptible motor neurons.
- Machine learning flagged dysregulation of VGF, INA, and PENK as strong predictors across species and SOD1 mutations, proposing biomarker candidates that now warrant validation in human cohorts.