Initiator | Metabolic defect | Metabolic mediator | Functional mediator | Consequence |
↑ Glucose | Glycation/AGE | Protein cross-linking | Matrix defects | Endoneurial fibrosis ↓ Neurotrophic SAM |
Protein inactivation | Receptor-ligand defects | ↓ Neurotrophism | ||
NO quenching | Vasoconstriction | Ischemia/hypoxia | ||
Macrophage activation | Cytokines, ↑ TGF | Cytotoxicity* Endoneurial fibrosis | ||
Free radical formation | Oxidative stress | Cytotoxicity | ||
Autooxidation | Free radical formation | Oxidative stress | Cytotoxicity* | |
↑ Sorbitol pathway | ↓ NADPH | Oxidative stress ↓ NO synthesis | Cytotoxicity* Ischemia/hypoxia | |
NADH/lactate | Pseudohypoxia | Cytotoxicity* | ||
↑ Glycation | (See above) | (See above) | ||
↓ Taurine | Oxidative stress | Cytotoxicity* | ||
↓ MI/↓ PI/↓ PKC | Signal transduction Eicosanoid defects | ↓ Neurotrophism Ischemia/hypoxia | ||
↑ DAG | ↑ PKC | Signal transduction | Ischemia | |
FA defects | ↑ Free FA | ↑ Long-chain acyl-Co's | Mitochondrial defects | Cytotoxicity |
↓ 3-β-dehydrog | ↓ GLA | Eicosanoid defects | Ischemia/hypoxia | |
↓ Insulin | ?↓ GF expression | ?IGF/NGF/BDNF/NT3 | Neurotrophic factors | ↓ Neurotrophism |
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