TY - JOUR
T1 - The neurovascular unit in leukodystrophies
T2 - towards solving the puzzle
AU - Zarekiani, Parand
AU - Nogueira Pinto, CH
AU - Hol, E.M.
AU - Bugiani, M
AU - de Vries, HE
N1 - Funding Information: PZ and MB are funded by the ZonMW Veni Grant #016.196.107. HNP, EMH and HEdV are funded by the NWO HMM2.0 CONNECT Grant #18957. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The neurovascular unit (NVU) is a highly organized multicellular system localized in the brain, formed by neuronal, glial (astrocytes, oligodendrocytes, and microglia) and vascular (endothelial cells and pericytes) cells. The blood-brain barrier, a complex and dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma, is a component of the NVU. In a variety of neurological disorders, including Alzheimer's disease, multiple sclerosis, and stroke, dysfunctions of the NVU occurs. There is, however, a lack of knowledge regarding the NVU function in leukodystrophies, which are rare monogenic disorders that primarily affect the white matter. Since leukodystrophies are rare diseases, human brain tissue availability is scarce and representative animal models that significantly recapitulate the disease are difficult to develop. The introduction of human induced pluripotent stem cells (hiPSC) now makes it possible to surpass these limitations while maintaining the ability to work in a biologically relevant human context and safeguarding the genetic background of the patient. This review aims to provide further insights into the NVU functioning in leukodystrophies, with a special focus on iPSC-derived models that can be used to dissect neurovascular pathophysiology in these diseases.
AB - The neurovascular unit (NVU) is a highly organized multicellular system localized in the brain, formed by neuronal, glial (astrocytes, oligodendrocytes, and microglia) and vascular (endothelial cells and pericytes) cells. The blood-brain barrier, a complex and dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma, is a component of the NVU. In a variety of neurological disorders, including Alzheimer's disease, multiple sclerosis, and stroke, dysfunctions of the NVU occurs. There is, however, a lack of knowledge regarding the NVU function in leukodystrophies, which are rare monogenic disorders that primarily affect the white matter. Since leukodystrophies are rare diseases, human brain tissue availability is scarce and representative animal models that significantly recapitulate the disease are difficult to develop. The introduction of human induced pluripotent stem cells (hiPSC) now makes it possible to surpass these limitations while maintaining the ability to work in a biologically relevant human context and safeguarding the genetic background of the patient. This review aims to provide further insights into the NVU functioning in leukodystrophies, with a special focus on iPSC-derived models that can be used to dissect neurovascular pathophysiology in these diseases.
KW - Astrocyte
KW - Blood–brain barrier
KW - Endothelium
KW - In vitro models
KW - Induced pluripotent stem cells
KW - Leukodystrophies
KW - Microglia
KW - Neurovascular unit
KW - Pericyte
UR - http://www.scopus.com/inward/record.url?scp=85125594630&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12987-022-00316-0
DO - https://doi.org/10.1186/s12987-022-00316-0
M3 - Review article
C2 - 35227276
SN - 2045-8118
VL - 19
SP - 18
JO - Fluids and barriers of the CNS
JF - Fluids and barriers of the CNS
IS - 1
M1 - 18
ER -