Defective translation initiation causes vanishing of cerebral white matter.
Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited white-matter disorders, especially in Caucasian populations. VWM is unusual because of its sensitivity to febrile infections and minor head trauma. The basic defect of this enigmatic brain disease resides in the regulation of initiation of protein synthesis. Recently, undue activation of the unfolded-protein response has emerged as an important factor in the pathophysiology of VWM. Here, we discuss the mechanisms that might be responsible for the selective involvement of the brain white matter in VWM. At present, VWM research is in need of an animal model to study disease mechanisms and therapeutic interventions.
Scheper
Gert C
GC
Department of Pediatrics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. gc.scheper@vumc.nl
Proud
Christopher G
CG
van der Knaap
Marjo S
MS
D000818:Animals; D001927:Brain Diseases / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism* / Q000502:physiology; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D014176:Protein Biosynthesis
D015852:Eukaryotic Initiation Factor-2; D020717:Eukaryotic Initiation Factor-2B