Restoring early postnatal synaptic dysregulation rescues motor neuron degeneration in a mouse model of Spinal and Bulbar Muscular Atrophy - PubMed
6 hours ago
- #neurodegeneration
- #SBMA
- #synaptic dysregulation
- Polyglutamine-expanded androgen receptor (AR) accumulates in motor neuron nuclei and upregulates glutamatergic synaptic genes via dysfunction of the transcriptional repressor REST during early postnatal development in SBMA model mice.
- Intervening in the neonatal period by reducing mutant AR or restoring REST function with antisense oligonucleotides mitigated gene dysregulation, improved disease phenotype, and reduced histopathology in AR-97Q mice.
- SBMA patient-derived iPSC motor neurons showed increased calcium activity and neuronal hyperexcitability, indicating early synaptic defects contribute to late-onset neurodegeneration as potential therapeutic targets.