Peripheral Neuropathy in Metabolic Stress

It has been broadly recognized that the nervous system is intertwined with various aspects of the body's metabolism. However, research over the past decade has unexpectedly revealed the involvement of the key metabolic coenzyme nicotinamide adenine dinucleotide (NAD⁺) and its degrading protein sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) in the central mechanism of pathological axon degeneration, which is the hallmark of peripheral neuropathy. Moreover, the recent implementation of state-of-the-art imaging techniques has achieved the comprehensive assessment of neuroanatomy in major metabolic organs, e.g., liver and adipose tissues, demonstrating that local neural inputs exhibit profound neuropathic changes under metabolic stress, some of which depend on the NAD⁺/SARM1 signal pathway. Here, we summarize current knowledge of the intrinsic link between pathological axon degeneration and metabolic stress and its actions in metabolic organs. In addition, we highlight critical questions regarding this new theme of neurometabolism that call for future research.