Mid1 is associated with androgen-dependent axonal vulnerability of motor neurons in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is a hereditary neurodegenerative disease caused by expansions of CAG repeats in the androgen receptor (AR) gene. Androgen-dependent nuclear accumulation of pathogenic AR protein causes degeneration of lower motor neurons, leading to progressive muscle weakness and atrophy. The study found upregulation of Mid1, a microtubule-associated RNA binding protein, in motor neurons of SBMA mice. Mid1 facilitates the translation of CAG-expanded mRNAs, including the pathogenic AR protein. Using spinal cord slice cultures from SBMA mouse fetuses, the study showed that Mid1 overexpression exacerbated androgen-dependent impairment of axonal regeneration, while Mid1 knockdown ameliorated it, suggesting Mid1 contributes to motor neuron vulnerability in SBMA.

• 1
  Mid1 is upregulated in the spinal motor neurons of SBMA mice and in samples from SBMA patients.
• 2
  Mid1 increases the protein levels of pathogenic AR with expanded CAG repeats in a cellular model of SBMA.
• 3
  Mid1 exacerbates the androgen-dependent impairment of axonogenesis in spinal cord slice cultures from SBMA mice, while Mid1 knockdown ameliorates it.