160 Chapter 7 Table 1. Astrocyte involvement in white matter CNS diseases (continued) Disease Pathology Detrimental impact on astrocytes Beneficial impact on astrocytes Ref Mitochondrial Leber’s hereditary optic neuropathy Loss of retinal ganglion cells, optic nerve degeneration. Unknown Unknown DNA repair defects Cockayne syndrome Patchy myelin loss, neuronal loss, astrocytic gliosis, microglia nodules. Multinucleated astrocytes Unknown 48 Defects in myelin genes PMD PLP1 duplication or gene alterations, dysmyelination, failure to form myelin. Increased astrocytic activity, astrogliosis. Unknown 49 AA / organic acid metabolism disorders Canavan disease Mutations of aspartoacylase gene. Diffuse spongiform white matter degeneration, dysmyelination and intramyelinic oedema. Hypertrophy and hyperplasia of astrocytes. Metabolic disturbance of mitochondria in abnormal astrocyte Unknown 50,51 Miscellaneous Alexander disease Myelin damage, Rosenthal fibres, nonneoplastic astrocytes Mutations in GFAP lead to diminished glutamate transporter, accumulation of CD44, and loss of EAAT-2. Loss of Cx43 and Cx30 Unknown 52 VWM Progressive demyelination, blunted dysmorphic astrocytes. Failure to reach maturity of astrocytes. Overexpression of nestin and GFAPδ Unknown 53 CADASIL Diffuse white matter lesions, subcortical infarcts. Granular osmiophilic material in small vessels Astrocytes undergo autophagy-like cell death. Glia-vascular unit damaged, BBB disturbed Unknown 54 PMLD Lack of the gap junction protein Cx47 leads to splitting and decompaction of myelin sheaths and axonal spheroids. Gap junctions between astrocytes and oligodendrocytes are disturbed compromising oligodendrocyte survival and myelination. Unknown 55 Abbreviations: ADEM, acute disseminated encephalomyelitis; AHL, acute haemorrhagic leukoencephalopathy; AQP4, Aquaporin-4; BBB, blood brain barrier; BDNF, Brain-derived neurotrophic factor; CMV, cytomegalovirus; CNS, central nervous system; EAAT, Excitatory amino acid transporter; GFAP, Glial fibrillary acidic protein; IGF, insulin-like growth factor; MLD, Metachromatic leukodystrophy; MS, multiple sclerosis; NMO, neuromyelitis optica; OPC, oligodendrocyte precursor cell; PDGF, platelet derived growth factor; PMD, Pelizaeus-Merzbacher disease; PMLD, Pelizae-
RkJQdWJsaXNoZXIy MTk4NDMw