| Developmental changes during myelination . | Potential maladaptive changes during demyelination . |
|---|---|
| Formation of nodes of Ranvier and paranodal junctions | Declustering of voltage-gated sodium channels, accumulation of intracellular sodium, failure of the Na+/K+ ATPase, accumulation of calcium through NCX reversal, and/or glutamate excitotoxicity and impairment of axon transport |
| Alterations in the phosphorylation states of cytoskeletal and axon transport-associated proteins | Dephosphorylation of microtubule-associated proteins following the loss of MAG and other myelin-derived signals, changes in microtubule stability potentially leading to cytoskeletal fragmentation or alterations in axon transport, and phosphorylation and inhibition of kinesin light chain |
| Development of the actin–spectrin cytoskeleton appears to be independent of myelination | Spectrin degradation and loss of actin–spectrin periodicity, loss of structural organization for cytoskeletal-associated proteins, declustering and mislocalization of voltage-gated sodium channels, mechanical instability, and perturbed interaction with the microtubule network leading to impaired axon transport |
| Dependence on myelinating glia for metabolic support | Progressive inability to maintain metabolic homeostasis in the setting of declustered voltage-gated sodium channels, impaired axon transport, cytoskeletal fragmentation, and aberrant ion concentration gradients |
| Developmental changes during myelination . | Potential maladaptive changes during demyelination . |
|---|---|
| Formation of nodes of Ranvier and paranodal junctions | Declustering of voltage-gated sodium channels, accumulation of intracellular sodium, failure of the Na+/K+ ATPase, accumulation of calcium through NCX reversal, and/or glutamate excitotoxicity and impairment of axon transport |
| Alterations in the phosphorylation states of cytoskeletal and axon transport-associated proteins | Dephosphorylation of microtubule-associated proteins following the loss of MAG and other myelin-derived signals, changes in microtubule stability potentially leading to cytoskeletal fragmentation or alterations in axon transport, and phosphorylation and inhibition of kinesin light chain |
| Development of the actin–spectrin cytoskeleton appears to be independent of myelination | Spectrin degradation and loss of actin–spectrin periodicity, loss of structural organization for cytoskeletal-associated proteins, declustering and mislocalization of voltage-gated sodium channels, mechanical instability, and perturbed interaction with the microtubule network leading to impaired axon transport |
| Dependence on myelinating glia for metabolic support | Progressive inability to maintain metabolic homeostasis in the setting of declustered voltage-gated sodium channels, impaired axon transport, cytoskeletal fragmentation, and aberrant ion concentration gradients |