<unk>  is a leukodystrophy which has unique biochemical abnormalities. A unique characteristic of<unk>  is that only oligodendrocytes and astrocytes are negatively affected<unk>  other glial cells and neurons seem to be unaffected. This is the central question behind<unk> . The real reasons behind this behavior are unknown since the cells are in the brain and have been rarely studied. However, there is a theory which is generally accepted by most experts in the field. The main characteristic of these cells is the fact that they synthesize a lot of proteins. These cells produce a large amount of proteins from a small amount of precursors and so are constantly working and under a reasonable amount of stress. So with a mutation in eIF2B, slight increases in the amount of stress these cells encounter occur, making them more susceptible to failure due to stress. The large amount of oligodendrocytes which display apoptotic characteristics and express apoptotic proteins suggests cell number reduction in the early stages of the disease. Premature ovarian failure has also been associated with diminishing<unk><unk> . However through an intensive survey, it was determined that even if an individual has premature ovarian failure, she does not necessarily have<unk> . eIF2B's role Overview of eIF2 and eIF2B's purpose in cells eIF2B is the guanine nucleotide-exchange factor for eIF2, and is composed of 5 subunits. The largest subunit, eIF2B5 contains the most mutations for<unk> . eIF2B is a complex which is very involved with the regulation of in the translation of mRNA into proteins. eIF2B is essential for the exchange of guanosine diphosphate(GDP) for guanosine-5'-triphosphate(GTP) in the initiation of translation via eIF2, because eIF2 is regenerated through this exchange. A decrease in eIF2B activity has been correlated with the onset of<unk> . A common factor among<unk>  patients is mutations in the five subunits of eIF2B (21 discovered thus far), expressed in over 60% of the patients. These mutations lead to the decreased activity of eIF2B. The most common mutation is R113H, which is the mutation of histidine to arginine. The homozygous form of the mutation is the least severe form. This mutation has also been documented in rodents, but they do not acquire<unk> ,<unk>  humans do. Another common mutation is G584A found in the eIF2B5 subunit. A correlation with stress has also been made, as eIF2B plays a central role in stress management – it is essential in down regulation protein synthesis in different stress conditions – and<unk>  patients are highly sensitive to stress. Protein eIF2B exists in all cells, and if this protein is reduced enough the cell will be negatively affected, and if it is reduced to zero, the cell will die. In affected cells, the protein is reduced to about 50%, which is acceptable for functionality in most cells, but not in glial cells since they synthesize a large amount of proteins constantly and need as many functioning proteins within them as possible. This would lower the baseline of the amount of stress a cell can handle, and thus in a stressed environment, it would have detrimental effects on these cells. Mutations in three of the subunits of eIF2B (2,4,&5) has been seen in both<unk>  and premature ovarian failure. The North American Cree population has also been found to have a distinctive mutation, R195H, which can lead to<unk> . All patients who have been studied only have one mutation present in the gene, causing the eIF2B to still be active, which leads to<unk> . If two mutations occurred, then eIF2B activity would be stopped by the body.
Leukoencephalopathy with vanishing white matter
Leukoencephalopathy with neuroaxonal spheroids
Megalencephalic leukoencephalopathy with subcortical cysts
Neurodegeneration with brain iron accumulation
Diffuse intrinsic pontine glioma
Hypertensive leukoencephalopathy
Wernicke encephalopathy
Camel spongiform encephalopathy