Dendrimer D5 is a Vector for Peptide Transport to Brain Cells

Саранцева, С. В.; Bolshakova, O. I.; Тимошенко, С. И.; Kolobov, A. A.; Schwarzman, A. L.

doi:10.1007/s10517-011-1160-z

Cited by 8 publications

(7 citation statements)

References 11 publications

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“…The cost of performing these trials in invertebrates would be comparatively small and would therefore allow for a much broader scaled testing strategy than can be applied to vertebrate systems. The use of Drosophila to address the problem of brain drug delivery was shown by Sarantseva et al ( 2011 ), where they tested the ability of dendrimers to cross the BBB. Dendrimers are nanopolymers that can encapsulate various cargo and therefore have been utilized in many biological (and non-biological) fields (see Kesharwani et al, 2014 for a review).…”

Section: The Invertebrate Bbb As a Tool For Advancing Therapeutic Intmentioning

confidence: 99%

“…The use of these biological vectors in drug delivery have been shown for epithelial barriers, such as the skin and intestine (e.g., Kaminskas et al, 2012 ). Moreover, the ability of the lysine-based dendrimer D5 to carry peptides across the Drosophila BBB has been shown (Sarantseva et al, 2011 ), suggesting that this nanotechnology could be a useful strategy for improving CNS drug delivery in vertebrates.…”

Section: The Invertebrate Bbb As a Tool For Advancing Therapeutic Intmentioning

confidence: 99%

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Barrier mechanisms in the Drosophila blood-brain barrier

2014

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The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through G-protein coupled receptor signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate BBB has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the BBB can govern whole animal physiologies. This includes novel functions of BBB gap junctions in orchestrating synchronized neuroblast proliferation, and of BBB secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate BBB anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

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Section: The Invertebrate Bbb As a Tool For Advancing Therapeutic Intmentioning

confidence: 99%

Section: The Invertebrate Bbb As a Tool For Advancing Therapeutic Intmentioning

confidence: 99%

Barrier mechanisms in the Drosophila blood-brain barrier

2014

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“…Drosophila is already a widely in vivo model used to disentangle the mechanisms and properties as well as dysfunctions of BBB of CNS disorders [143,[189][190][191]. Moreover, different approaches are available to evaluate the capacity of drugs to cross the fly BBB, making this model suitable for preclinical drug screening [148,160,192].…”

Section: Drosophila Bbb As a Tool For Cns Treatments Discoverymentioning

confidence: 99%

Exploiting the Potential of Drosophila Models in Lysosomal Storage Disorders: Pathological Mechanisms and Drug Discovery

et al. 2021

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Lysosomal storage disorders (LSDs) represent a complex and heterogeneous group of rare genetic diseases due to mutations in genes coding for lysosomal enzymes, membrane proteins or transporters. This leads to the accumulation of undegraded materials within lysosomes and a broad range of severe clinical features, often including the impairment of central nervous system (CNS). When available, enzyme replacement therapy slows the disease progression although it is not curative; also, most recombinant enzymes cannot cross the blood-brain barrier, leaving the CNS untreated. The inefficient degradative capability of the lysosomes has a negative impact on the flux through the endolysosomal and autophagic pathways; therefore, dysregulation of these pathways is increasingly emerging as a relevant disease mechanism in LSDs. In the last twenty years, different LSD Drosophila models have been generated, mainly for diseases presenting with neurological involvement. The fruit fly provides a large selection of tools to investigate lysosomes, autophagy and endocytic pathways in vivo, as well as to analyse neuronal and glial cells. The possibility to use Drosophila in drug repurposing and discovery makes it an attractive model for LSDs lacking effective therapies. Here, ee describe the major cellular pathways implicated in LSDs pathogenesis, the approaches available for their study and the Drosophila models developed for these diseases. Finally, we highlight a possible use of LSDs Drosophila models for drug screening studies.

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“…63,64 The data of Kim et al are supported by results on efficient dendrimer-mediated delivery into the brain through the blood-brain barrier. 63,64 Dendrimers can deliver genetic material, [65][66][67] peptides, 68 or the anticancer drug paclitaxel to the brain. 69 Moreover, PAMAM dendrimers can restore blood-brain barrier permeability in rats with diabetes mellitus.…”

Section: Dendrimersmentioning

confidence: 99%