2-Arachidonoylglycerol Reduces Proteoglycans and Enhances Remyelination in a Progressive Model of Demyelination

Multiple sclerosis (MS) is characterized by inflammation, demyelination, axonal damage, and gliosis. Remyelination, the repair process, becomes less efficient as the disease progresses, leading to disability. Chondroitin sulfate proteoglycans (CSPGs) accumulate in demyelinated areas, inhibiting neuronal growth and remyelination. This study explores the role of 2-arachidonoylglycerol (2-AG), an endocannabinoid, in modulating CSPG deposition. The study found that inhibiting 2-AG hydrolysis reduces CSPG accumulation, promotes remyelination, and improves motor function in a mouse model of MS, suggesting a potential therapeutic strategy.

• 1
  Inhibition of 2-AG hydrolysis reduces CSPGs accumulation and astrogliosis around demyelinated lesions in the spinal cord of Theiler’s murine encephalomyelitis virus-infected mice.
• 2
  Inhibition of 2-AG hydrolysis augments the number of mature oligodendrocytes and increases MBP, leading to remyelination and functional recovery of mice.
• 3
  The motor function improvement elicited by UCM03025 was reverted significantly by the CB1 or CB2 receptor antagonists when administered individually or together