TY - JOUR
T1 - Astrocyte–Oligodendrocyte–Microglia Crosstalk in Astrocytopathies
AU - de Waard, Dieuwke Maria
AU - Bugiani, Marianna
PY - 2020/11/19
Y1 - 2020/11/19
N2 - Defective astrocyte function due to a genetic mutation can have major consequences for microglia and oligodendrocyte physiology, which in turn affects the white matter integrity of the brain. This review addresses the current knowledge on shared and unique pathophysiological mechanisms of astrocytopathies, including vanishing white matter, Alexander disease, megalencephalic leukoencephalopathy with subcortical cysts, Aicardi–Goutières syndrome, and oculodentodigital dysplasia. The mechanisms of disease include protein accumulation, unbalanced secretion of extracellular matrix proteins, pro- and anti-inflammatory molecules, cytokines and chemokines by astrocytes, as well as an altered gap junctional network and a changed ionic and nutrient homeostasis. Interestingly, the extent to which astrogliosis and microgliosis are present in these astrocytopathies is highly variable. An improved understanding of astrocyte–microglia–oligodendrocyte crosstalk might ultimately lead to the identification of druggable targets for these, currently untreatable, severe conditions.
AB - Defective astrocyte function due to a genetic mutation can have major consequences for microglia and oligodendrocyte physiology, which in turn affects the white matter integrity of the brain. This review addresses the current knowledge on shared and unique pathophysiological mechanisms of astrocytopathies, including vanishing white matter, Alexander disease, megalencephalic leukoencephalopathy with subcortical cysts, Aicardi–Goutières syndrome, and oculodentodigital dysplasia. The mechanisms of disease include protein accumulation, unbalanced secretion of extracellular matrix proteins, pro- and anti-inflammatory molecules, cytokines and chemokines by astrocytes, as well as an altered gap junctional network and a changed ionic and nutrient homeostasis. Interestingly, the extent to which astrogliosis and microgliosis are present in these astrocytopathies is highly variable. An improved understanding of astrocyte–microglia–oligodendrocyte crosstalk might ultimately lead to the identification of druggable targets for these, currently untreatable, severe conditions.
KW - Aicardi–Goutières syndrome
KW - Alexander disease
KW - astrocytopathies
KW - cellular crosstalk
KW - megalencephalic leukoencephalopathy with subcortical cysts
KW - oculodentodigital dysplasia
KW - vanishing white matter
UR - http://www.scopus.com/inward/record.url?scp=85097250109&partnerID=8YFLogxK
U2 - 10.3389/fncel.2020.608073
DO - 10.3389/fncel.2020.608073
M3 - Review article
VL - 14
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
M1 - 608073
ER -