Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies

Astrocytes, the main Central Nervous System (CNS) glial cell type, actively release transmitters, including glutamate, and thereby participate in physiological brain information processing. However, dysregulated transmitter release from astrocytes can contribute to CNS disease pathogenesis and prog...

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Main Authors: Roberta de Ceglia, Andrea Volterra
Format: Article
Language:deu
Published: Swiss Chemical Society 2022-12-01
Series:CHIMIA
Subjects:
Online Access:https://chimia.ch/chimia/article/view/6172
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author Roberta de Ceglia
Andrea Volterra
author_facet Roberta de Ceglia
Andrea Volterra
author_sort Roberta de Ceglia
collection DOAJ
description Astrocytes, the main Central Nervous System (CNS) glial cell type, actively release transmitters, including glutamate, and thereby participate in physiological brain information processing. However, dysregulated transmitter release from astrocytes can contribute to CNS disease pathogenesis and progression. Therefore, targeting astrocyte glutamate release is a promising new therapeutic strategy in hyper-glutamatergic brain conditions, as it does not directly block glutamatergic neurotransmission. Basing on the evidence that astrocytes express Vesicular Glutamate Transporters (VGLUT), in collaboration with other NCCR TransCure partners, we developed an innovative approach for astrocyte-selective delivery of nanobodies inhibiting VGLUT. We inserted the anti-VGLUT nanobody constructs in astrocyte-directed viral vectors that were administered peripherally, crossed the blood-brain-barrier and led to successful cell-specific CNS-wide expression of the nanobodies.
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spelling doaj.art-e9ae9b316c844ff79c5dd4c7ec98fbb92023-02-12T01:02:19ZdeuSwiss Chemical SocietyCHIMIA0009-42932673-24242022-12-01761210.2533/chimia.2022.1033Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory NanobodiesRoberta de Ceglia0Andrea Volterra1Department of Fundamental Neurosciences, University of LausanneDepartment of Fundamental Neutrosciences, University of Lausanne; Wyss Center, Chemin des Mines 9, Geneva Astrocytes, the main Central Nervous System (CNS) glial cell type, actively release transmitters, including glutamate, and thereby participate in physiological brain information processing. However, dysregulated transmitter release from astrocytes can contribute to CNS disease pathogenesis and progression. Therefore, targeting astrocyte glutamate release is a promising new therapeutic strategy in hyper-glutamatergic brain conditions, as it does not directly block glutamatergic neurotransmission. Basing on the evidence that astrocytes express Vesicular Glutamate Transporters (VGLUT), in collaboration with other NCCR TransCure partners, we developed an innovative approach for astrocyte-selective delivery of nanobodies inhibiting VGLUT. We inserted the anti-VGLUT nanobody constructs in astrocyte-directed viral vectors that were administered peripherally, crossed the blood-brain-barrier and led to successful cell-specific CNS-wide expression of the nanobodies. https://chimia.ch/chimia/article/view/6172AstrocyteCell-specific viral vectorsNanobodyVGLUT
spellingShingle Roberta de Ceglia
Andrea Volterra
Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
CHIMIA
Astrocyte
Cell-specific viral vectors
Nanobody
VGLUT
title Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
title_full Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
title_fullStr Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
title_full_unstemmed Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
title_short Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies
title_sort vesicular glutamate transporters in astrocytes as potential new therapeutic targets astrocyte targeted viral vectors expressing inhibitory nanobodies
topic Astrocyte
Cell-specific viral vectors
Nanobody
VGLUT
url https://chimia.ch/chimia/article/view/6172
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