Critical Role of Astrocyte NAD1 Glycohydrolase in Myelin Injury and Regeneration

This study investigates how a high-fat diet impacts myelin, the protective coating around nerve fibers, and the cells that produce it (oligodendrocytes). The research focuses on the role of astrocytes, a type of brain cell, and a specific enzyme called CD38 in this process. The study found that a high-fat diet increases CD38 activity in astrocytes, leading to reduced levels of a crucial molecule called NAD1. This, in turn, harms oligodendrocytes and impairs myelin regeneration. By inhibiting CD38, either genetically or with a drug, the researchers were able to protect oligodendrocytes, restore NAD1 levels, and promote myelin repair, suggesting a potential therapeutic target for diseases like multiple sclerosis.

• 1
  High-fat diet consumption increases CD38 expression in astrocytes, leading to NAD1 depletion in the spinal cord.
• 2
  Genetic inactivation of CD38 protects mice from high-fat diet-induced oligodendrocyte loss, neuroinflammation, and oxidative damage.
• 3
  Pharmacological inhibition of CD38 with 78c enhances myelin regeneration in a lysolecithin-induced demyelination model and skews astrocytes toward a pro-repair phenotype.