Ascorbate and its transporter SVCT2: The dynamic duo's integrated roles in CNS neurobiology and pathophysiology

Ascorbate is a small antioxidant molecule essential for the proper development and function of the brain. Ascorbate is transported into the brain and between brain cells via the Sodium vitamin C co-transporter 2 (SVCT2). This review provides an in-depth analysis of ascorbate's physiology, including how ascorbate is absorbed from food into the CNS, emphasizing cellular mechanisms of ascorbate recycling and release in different CNS compartments. Additionally, the review delves into the various functions of ascorbate in the CNS, including its impact on epigenetic modulation, synaptic plasticity, and neurotransmission. It also emphasizes ascorbate's role on neuromodulation and its involvement in neurodevelopmental processes and disorders. Furthermore, it analyzes the relationship between the duo ascorbate/SVCT2 in neuroinflammation, particularly its effects on microglial activation, cytokine release, and oxidative stress responses, highlighting its association with neurodegenerative diseases, such as Alzheimer's disease (AD). Overall, this review emphasizes the crucial role of the dynamic duo ascorbate/SVCT2 in CNS physiology and pathology and the need for further research to fully comprehend its significance in a neurobiological context and its potential therapeutic applications.