Arginine Methyltransferase PRMT8 Provides Cellular Stress Tolerance in Aging Motoneurons

Aging and cellular stress can lead to neurodegeneration. This study identifies a protective mechanism in spinal cord motoneurons involving a high abundance of asymmetric dimethyl arginines (ADMAs), which provide protection against environmental stress. Protein arginine methyltransferase 8 (PRMT8) is identified as the enzyme responsible for maintaining ADMA levels in these neurons. Mice lacking PRMT8 exhibit decreased muscle strength with age due to destabilization of neuromuscular junctions. Loss of PRMT8 function leads to accumulation of unrepaired DNA damage and decreased levels of CREB1, a protein that promotes cell survival and regeneration. This dysregulation contributes to motoneuron degeneration.

• 1
  Spinal cord motoneurons exhibit high levels of asymmetric dimethyl arginines (ADMAs), providing protection against environmental stress.
• 2
  PRMT8 is a tissue-restricted enzyme responsible for maintaining proper ADMA levels in postmitotic neurons. Loss of PRMT8 leads to decreased muscle strength and destabilization of neuromuscular junctions in aging mice.
• 3
  Inhibition of PRMT8 results in accumulation of unrepaired DNA double-stranded breaks, decreased CREB1 levels, and dysregulation of prosurvival and regeneration-associated genes.