Lactate, an underestimated molecule in nerve regeneration

Lactate, a crucial metabolite, plays an important role in the nervous system. It not only serves as an intermediate in energy metabolism but also exhibits significant neuroregenerative and neuroprotective properties. This review summarizes the multifaceted roles of lactate in neuroregeneration. First, lactate is involved in both neural damage and protection through lactylation. Second, the two subunits of lactate dehydrogenase (LDH) are respectively involved in damage and protection processes. Meanwhile, the expression and activity of monocarboxylate transporters (MCTs) collectively regulate neuronal energy metabolism and lactate shuttle, thereby influencing neuroregeneration. Furthermore, lactate accelerates axonal growth by modulating growth cone dynamics and guidance, thereby promoting neuroregeneration. Additionally, lactate possesses antioxidant and anti-inflammatory properties, protecting neurons from oxidative stress and inflammatory damage, which further supports neuroregeneration. Although the role of lactate in neuroregeneration is increasingly recognized, its underlying molecular mechanisms require further elucidation. Its potential therapeutic applications in both the central and peripheral nervous systems warrant in-depth investigation.