摘要
Myelination by oligodendroglial cells （OLs） enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders. However, accumulating evidence indicates that OLs also provide support to neurons via mechanisms beyond the insulating function of myelin. More im- portantly, an increasing volume of reports indicates defects of OLs in numerous neurodegenerative diseases, sometimes even preceding neuronal loss in pre-symptomatic episodes, suggesting that OL pathology may be an important mechanism contributing to the initiation and/or progression of neurodegeneration. This review fo- cuses on the emerging picture of neuronal support by OLs in the pathogenesis of neurodegenerative disorders through diverse molecular and cellular mechanisms, including direct neuron-myelin interaction, metabolic sup- port by OLs, and neurotrophic factors produced by and/or acting on OLs.
Myelination by oligodendroglial cells （OLs） enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders. However, accumulating evidence indicates that OLs also provide support to neurons via mechanisms beyond the insulating function of myelin. More im- portantly, an increasing volume of reports indicates defects of OLs in numerous neurodegenerative diseases, sometimes even preceding neuronal loss in pre-symptomatic episodes, suggesting that OL pathology may be an important mechanism contributing to the initiation and/or progression of neurodegeneration. This review fo- cuses on the emerging picture of neuronal support by OLs in the pathogenesis of neurodegenerative disorders through diverse molecular and cellular mechanisms, including direct neuron-myelin interaction, metabolic sup- port by OLs, and neurotrophic factors produced by and/or acting on OLs.
基金
supported by NIH grants NS070526 and NS056097 to YF,and NS070526-01A1S1 to MDM
ANB and MDM were supported by NIH training grant T32GM008602
