scholarly journals An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein

Cell Reports ◽  
2021 ◽  
Vol 35 (10) ◽  
pp. 109189
Author(s):  
Eleanna Kara ◽  
Alessandro Crimi ◽  
Anne Wiedmer ◽  
Marc Emmenegger ◽  
Claudia Manzoni ◽  
...  
Keyword(s):  
Cell Transfer ◽  
Genomic Approach ◽  
Genetic Landscape ◽  
Cell To Cell Transfer

scholarly journals An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein

2019 ◽  
Author(s):  
Eleanna Kara ◽  
Alessandro Crimi ◽  
Anne Wiedmer ◽  
Marc Emmenegger ◽  
Claudia Manzoni ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Interaction Analysis ◽  
Supporting Evidence ◽  
Cell Transfer ◽  
Double Positive ◽  
Genome Wide ◽  
Genomic Approach ◽  
Genetic Overlap ◽  
Genetic Landscape ◽  
Cell To Cell Transfer

SummaryNeuropathological and experimental evidence suggests that the cell-to-cell transfer of a-synuclein has an important role in the pathogenesis of Parkinson’s disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook an siRNA, genome-wide high throughput screen to identify genes regulating the cell-to-cell transfer of a-synuclein. We transiently transfected HEK cells stably overexpressing a-synuclein with a construct encoding GFP-2a-aSynuclein-RFP. The cells expressing a-synuclein-RFP through transfection were double positive for GFP and RFP fluorescence, whereas the cells receiving it through transfer were positive only for RFP fluorescence. The amount of a-synuclein transfer was quantified by high content microscopy. A series of unbiased screens confirmed the involvement of 38 genes in the regulation of a-synuclein-RFP transfer. One of those hits was ITGA8, a candidate gene recently identified through a large PD genome wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) showed that the hits clustered in networks that included known PD Mendelian and GWAS risk genes more frequently than expected than random chance. Given the genetic overlap between a-synuclein transfer and PD, those findings provide supporting evidence for the importance of the cell-to-cell transfer of a-synuclein in the pathogenesis of PD, and expand our understanding of the mechanism of a-synuclein spread.

scholarly journals Evaluating the abilities of diverse nitroaromatic prodrug metabolites to exit a model Gram negative vector for bacterial-directed enzyme-prodrug therapy

2020 ◽  
Author(s):  
JVE Chan-Hyams ◽  
JN Copp ◽  
JB Smaill ◽  
AV Patterson ◽  
David Ackerley
Keyword(s):  
Human Cell ◽  
Bacterial Cell ◽  
Bystander Effect ◽  
Cell Transfer ◽  
Bacterial Strains ◽  
Enzyme Prodrug Therapy ◽  
E Coli ◽  
Human Cell Cultures ◽  
Cell To Cell Transfer ◽  
Nitro Reduction

© 2018 Elsevier Inc. Gene-directed enzyme-prodrug therapy (GDEPT) employs tumour-tropic vectors including viruses and bacteria to deliver a genetically-encoded prodrug-converting enzyme to the tumour environment, thereby sensitising the tumour to the prodrug. Nitroreductases, able to activate a range of promising nitroaromatic prodrugs to genotoxic metabolites, are of great interest for GDEPT. The bystander effect (cell-to-cell transfer of activated prodrug metabolites) has been quantified for some nitroaromatic prodrugs in mixed multilayer human cell cultures, however while these provide a good model for viral DEPT (VDEPT) they do not inform on the ability of these prodrug metabolites to exit bacterial vectors (relevant to bacterial-DEPT (BDEPT)). To investigate this we grew two Escherichia coli strains in co-culture; an activator strain expressing the nitroreductase E. coli NfsA and a recipient strain containing an SOS-GFP DNA damage responsive gene construct. In this system, induction of GFP by reduced prodrug metabolites can only occur following their transfer from the activator to the recipient cells. We used this to investigate five clinically relevant prodrugs: metronidazole, CB1954, nitro-CBI-DEI, and two dinitrobenzamide mustard prodrug analogues, PR-104A and SN27686. Consistent with the bystander efficiencies previously measured in human cell multilayers, reduced metronidazole exhibited little bacterial cell-to-cell transfer, whereas nitro-CBI-DEI was passed very efficiently from activator to recipient cells post-reduction. However, in contrast with observations in human cell multilayers, the nitrogen mustard prodrug metabolites were not effectively passed between the two bacterial strains, whereas reduced CB1954 was transferred efficiently. Using nitroreductase enzymes that exhibit different biases for the 2- versus 4-nitro substituents of CB1954, we further showed that the 2-nitro reduction products exhibit substantially higher levels of bacterial cell-to-cell transfer than the 4-nitro reduction products, consistent with their relative bystander efficiencies in human cell culture. Overall, our data suggest that prodrugs may differ in their suitability for VDEPT versus BDEPT applications and emphasise the importance of evaluating an enzyme-prodrug partnership in an appropriate context for the intended vector.

scholarly journals Distinct efficacy of HIV-1 entry inhibitors to prevent cell-to-cell transfer of R5 and X4 viruses across a human placental trophoblast barrier in a reconstitution model in vitro

Retrovirology ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. 31 ◽  
Author(s):  
Ahidjo Ayouba ◽  
Claude Cannou ◽  
Marie-Thérèse Nugeyre ◽  
Françoise Barré-Sinoussi ◽  
Elisabeth Menu
Keyword(s):  
Cell Transfer ◽  
Entry Inhibitors ◽  
Cell To Cell Transfer ◽  
Hiv 1

scholarly journals Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions

2005 ◽  
Vol 568 (2) ◽  
pp. 459-468 ◽  
Author(s):  
V. Valiunas ◽  
Y. Y. Polosina ◽  
H. Miller ◽  
I. A. Potapova ◽  
L. Valiuniene ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Specific Cell ◽  
Cell Transfer ◽  
Short Interfering Rna ◽  
Interfering Rna ◽  
Cell To Cell Transfer

Recycling of HIV Particles is Required for Infection by Endocytosed Virus after Cell to Cell Transfer

2011 ◽  
Vol 90 (2) ◽  
pp. A51
Author(s):  
Marc Permanyer ◽  
Ester Ballana ◽  
José A. Esté
Keyword(s):  
Cell Transfer ◽  
Cell To Cell Transfer

Genome-wide screen for Escherichia coli genes involved in repressing cell-to-cell transfer of non-conjugative plasmids

2012 ◽  
Vol 428 (4) ◽  
pp. 445-450 ◽  
Author(s):  
Ayako Matsuda ◽  
Naomi Kurono ◽  
Chinatsu Kawano ◽  
Kozue Shirota ◽  
Akiko Hirabayashi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Transfer ◽  
Conjugative Plasmids ◽  
Genome Wide ◽  
Cell To Cell Transfer

scholarly journals Cell-to-Cell Transfer of M. tuberculosis Antigens Optimizes CD4 T Cell Priming

2014 ◽  
Vol 15 (6) ◽  
pp. 741-752 ◽  
Author(s):  
Smita Srivastava ◽  
Joel D. Ernst
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Cell Transfer ◽  
T Cell Priming ◽  
Cell To Cell Transfer
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