Metabolic Symbiosis and Vulnerability in the CNS Axon-Myelin Unit

Axonal degeneration and demyelination are common pathological phenotypes in central nervous system (CNS) injury and degenerative diseases. Axonal and myelin diseases have generally been considered distinct phenomena, although our knowledge of why the axon-myelin unit (AMU), as a highly interconnected structure, serves as a common point of vulnerability to damage remains inadequate. In this review, we first reaffirm that the tight biological interconnections between axons and myelin should be recognized as a "symbiotic" unit across development, metabolism, and disease progression. Second, we systematically delineate the fundamental structural architecture and metabolic coupling of AMU. Third, we analyze how the impairment of one component of AMU influences the survival and functional integrity of others. In conclusion, we present a unique conceptual framework indicating that therapeutic methods targeting bioenergetic support in the CNS should concentrate on the energy coupling pathways and damage-crossover mechanisms of the AMU.