Journal ArticleDOI
Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
Annika Keller,Annika Keller,Annika Keller,Ana Westenberger,María Jesús Sobrido,María García-Murias,Aloysius Domingo,Renee L. Sears,R. R. Lemos,Andrés Ordóñez-Ugalde,Gaël Nicolas,José Eriton Gomes da Cunha,Elisabeth J. Rushing,Michael Hugelshofer,Moritz C. Wurnig,Andres Kaech,Regina Reimann,Katja Lohmann,Valerija Dobricic,Angel Carracedo,Igor Petrović,Janis M. Miyasaki,Irina Abakumova,Maarja Mäe,Maarja Mäe,Elisabeth Raschperger,Elisabeth Raschperger,Mayana Zatz,Katja Zschiedrich,Jörg Klepper,Elizabeth Spiteri,Elizabeth Spiteri,J.M. Prieto,I. Navas,Michael Preuss,Carmen Dering,Milena Jankovic,Martin Paucar,Per Svenningsson,Kioomars Saliminejad,Hamid Reza Khorram Khorshid,Ivana Novakovic,Adriano Aguzzi,Andreas Boss,Isabelle Le Ber,Gilles Defer,Didier Hannequin,Vladimir S. Kostic,Dominique Campion,Daniel H. Geschwind,Giovanni Coppola,Christer Betsholtz,Christer Betsholtz,Christine Klein,João Ricardo Mendes de Oliveira +54 more
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TLDR
The data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.Abstract:
Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor β (PDGF-Rβ) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-Rβ. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.read more
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Book ChapterDOI
An Update on Primary Familial Brain Calcification
TL;DR: In this article, mutations in the SLC20A2 gene coding for the inorganic phosphate transporter PiT2 were linked to PFBC, thereby implicating impaired phosphate transport as an underlying disease mechanism.
Journal ArticleDOI
Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor.
TL;DR: The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti‐PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment.
Journal ArticleDOI
Breaking and building the wall: the biology of the blood-brain barrier in health and disease.
TL;DR: The blood-brain barrier (BBB) is a complex feature of brain endothelial cells that restricts the passage of blood-borne molecules into the brain parenchyma, while ensuring the delivery of essential nutrients and selected biomolecules.
Journal ArticleDOI
Primary familial brain calcification: Genetic analysis and clinical spectrum
Ilaria Taglia,Andrea Mignarri,Simone Olgiati,Elisabetta Menci,Patrizia L. Petrocelli,Guido J. Breedveld,Cesa Scaglione,Paolo Martinelli,Antonio Federico,Vincenzo Bonifati,Maria Teresa Dotti +10 more
TL;DR: Primary familial brain calcification is a rare autosomal dominant disorder with bilateral calcification of basal ganglia and other cerebral regions, movement disorders, and neuropsychiatric disturbances.
Journal ArticleDOI
Primary Brain Calcification Causal PiT2 Transport-Knockout Variants can Exert Dominant Negative Effects on Wild-Type PiT2 Transport Function in Mammalian Cells.
TL;DR: In mammalian cells, the analyzed SLC20A2 missense variants can exert their effect in a dominant negative manner resulting in decreased wild-type PiT2 Pi transport, which may contribute to an earlier disease onset and/or a more severe phenotype as observed for Slc20a2−/− mice compared to Slc 20a2+/− mouse.
References
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Journal ArticleDOI
Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor
TL;DR: Structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role ofPDGF in normal and diseased tissues are discussed.
Journal ArticleDOI
Pericytes regulate the blood–brain barrier
Annika Armulik,Guillem Genové,Maarja Mäe,Maya H. Nisancioglu,Elisabet Wallgard,Elisabet Wallgard,Colin Niaudet,Liqun He,Liqun He,Jenny Norlin,Per Lindblom,Karin Strittmatter,Karin Strittmatter,Bengt Johansson,Christer Betsholtz +14 more
TL;DR: A novel and critical role for pericytes is indicated in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the blood–brain barrier.
Journal ArticleDOI
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
TL;DR: Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts, and endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells.
Journal ArticleDOI
Role of platelet-derived growth factors in physiology and medicine.
TL;DR: Basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts are reviewed.
Journal ArticleDOI
Pericytes are required for blood–brain barrier integrity during embryogenesis
TL;DR: Pericytes regulate functional aspects of the blood–brain barrier, including the formation of tight junctions and vesicle trafficking in CNS endothelial cells, but inhibit the expression of molecules that increase vascular permeability and CNS immune cell infiltration.
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