Fig. 3.

Cuprizone induced myelin loss could be due to reduced myelin protein production and the subsequent destabilization and vacuolation of the myelin sheath. (1) Cuprizone administration leads to reduced levels of certain amino acids (Glycine, Alanine, and Proline) in the blood plasma. This amino acid starvation could lead directly or indirectly – through the amino acid response pathway – to reduced protein synthesis in the oligodendrocyte. (2) In the cuprizone model several proteins are reduced, that are either part of the myelin sheath or enzymes that produce components of the myelin sheath. For example, MAG and MBP are reduced – both are crucial stabilizers of the myelin sheath. CGT and HMG-CoA reductase are reduced as well. CGT is crucial in producing Galactocerebrosides. HMG-CoA is involved in the cholesterol synthesis pathway. Both Galactocerebrosides and cholesterol are important parts of the myelin sheath membrane. Lack of MAG, MBP, galactocerebrosides, and cholesterol could lead to myelin sheath destabilization, formation of intramyelinic vacuoles, and subsequence myelin and axonal damage degradation