Abstract
Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.
Highlights
Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons
Alterations of oligodendrocytes and CNS myelin are a feature of several CNS pathologies including leukodystrophies, spinal cord injury, multiple sclerosis (MS; a chronic inflammatory demyelinating disease that leads to neurodegeneration) and other inflammatory demyelinating CNS disorders, periventricular leukomalacia, as well as several “classical” neurodegenerative disorders such as Alzheimer’s disease, etc. [8,9]
This review summarizes our current knowledge of energy metabolism pathways in oligodendroglial cells, how these may differ during the process of differentiation, and which energy sources might be crucial to sustainmyelination
Summary
Lipids are the major component of myelin membranes (70–80% of dry weight). The first step of fatty acid synthesis is the synthesis of palmitate from acetyl CoA. This process is fundamental in myelin generation, as the knockout of oligodendroglial fatty acid synthase, the enzyme complex that carries out this process, impairs myelin generation and repair [41]. As estimated by Harris and Attwell [42], if one takes into account the loss of ATP generation when acetyl CoA molecules are diverted from oxidative phosphorylation (ATP generation) to palmitate synthesis and glucose molecules are diverted to PPP from glycolysis (to generate NADPH required), the synthesis of palmitate costs 228 ATP molecules. Taking into account the normal lipid composition of myelin, the lipid production required for one gram of myelin was estimated to cost 3.24 × 1023 ATP molecules [42]
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