Unleashing metabolic power for axonal regeneration

HighlightsMetabolic changes are essential for axonal regeneration.Neurons may convert their inert metabolic state to an anabolic metabolism to support axon regrowth.Preconditioning injury in peripheral nerves endows neurons with a regenerative capacity associated with metabolic modification.Multiple growth factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF), promote axonal regeneration by stimulating the mechanistic target of rapamycin (mTOR) pathway and upregulating anabolic metabolism.Cellular metabolism and epigenetic modification are tightly interconnected and mutually regulated during axonal regeneration.AbstractAxon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function.