Autophagy and signaling: their role in cell survival and cell death

Codogno, Patrice; Meijer, Alfred J.

doi:10.1038/sj.cdd.4401751

Cited by 1,023 publications

(873 citation statements)

References 89 publications

(139 reference statements)

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“…Autophagy can lead to contrary cellular fates because it is involved in both beneficial and harmful cellular effects 44. While autophagy is activated at a basal level in most of the cells in the body with a role in regulating the turnover of long‐lived proteins and eliminating damaged structures, high levels of autophagy are often an indication of cellular stress.…”

Section: Resultsmentioning

confidence: 99%

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Moscariello

Jansen

et al. 2018

Advanced Science

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Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here.

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Section: Resultsmentioning

confidence: 99%

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Moscariello

Jansen

et al. 2018

Advanced Science

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“…However, these observations did not prove that autophagy played a death-promoting role in this type of cell death. To analyze a potential contributory role of autophagy in caspase-independent cell death induced by gossypol, we performed a lentiviral knockdown of both Beclin1 and Atg5 (7,9) in three different glioma cell lines (U87, MZ-54, and U343; Fig. 7A).…”

Section: Knockdown Of Beclin1 and Atg5 Protects Malignant Glioma Cellmentioning

confidence: 99%

“…The role of autophagy is highly contextual, as it can exert both cytoprotective and death-promoting effects, the latter of which implicating overactivation of autophagy as an alternative cell death pathway (9,10). Indeed, induction of autophagic cell death (type II cell death) by autophagy stimulators has been recently discussed as a concept to exploit caspase-independent programmed cell death pathways for the development of novel anticancer therapies, especially those directed against malignant gliomas (11,12).…”

Section: Introductionmentioning

confidence: 99%

The Pan-Bcl-2 Inhibitor (−)-Gossypol Triggers Autophagic Cell Death in Malignant Glioma

Voss

Senft

Lang

et al. 2010

Molecular Cancer Research

174

145

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Antiapoptotic Bcl-2 family members suppress both apoptosis and autophagy and are of major importance for therapy resistance of malignant gliomas. To target these molecules, we used BH3 mimetics and analyzed the molecular mechanisms of cell death induced thereby. Glioma cells displayed only limited sensitivity to single-agent treatment with the BH3 mimetics HA14-1, BH3I-2′, and ABT-737, whereas the pan-Bcl-2 inhibitor (−)-gossypol efficiently induced cell death. Furthermore, (−)-gossypol potentiated cell death induced by temozolomide (TMZ) in MGMT (O 6 -methylguanine-DNA methyltransferase)-negative U343 cells and, to a lesser extent, in MGMT-expressing U87 cells. (−)-Gossypol triggered translocation of light chain 3 to autophagosomes and lysosomes and cytochrome c release, but cell death occurred in the absence of lysosomal damage and effector caspase activation. Lentiviral knockdown of Beclin1 and Atg5 in U87, U343, and MZ-54 cells strongly diminished the extent of cell death induced by (−)-gossypol and combined treatment with TMZ, indicating that autophagy contributed to this type of cell death. In contrast, stable knockdown of the endogenous autophagy inhibitor mammalian target of rapamycin increased autophagic cell death. Our data suggest that pan-Bcl-2 inhibitors are promising drugs that induce caspase-independent, autophagic cell death in apoptosis-resistant malignant glioma cells and augment the action of TMZ. Furthermore, they indicate that efficient killing of glioma cells requires neutralization of Mcl-1.

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“…It is now clear this process has a dual role. 7 By contrast, autophagy is a degradative mechanism for long-lived proteins and damaged organelles through the auto-phago-lysosomal pathway and on the other, it provides possibility of self-destruction for cells. 4,5,8 In Drosophila, autophagy can be hormonally controlled by ecdysone; through inhibition of a class-I phosphatidyl-inositol 3-kinase (PI3K) pathway organs, such as the fat body, are eliminated at the end of larval stage.…”

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confidence: 99%

Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes

et al. 2007

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MCF-7 cells undergo autophagic death upon tamoxifen treatment. Plated on non-adhesive substratum these cells died by anoikis while inducing autophagy as revealed by monodansylcadaverine staining, elevated light-chain-3 expression and electron microscopy. Both de novo and anoikis-derived autophagic dying cells were engulfed by human macrophages and MCF-7 cells. Inhibition of autophagy by 3-methyladenine abolished engulfment of cells dying through de novo autophagy, but not those dying through anoikis. Blocking exposure of phosphatidylserine (PS) on both dying cell types inhibited phagocytosis by MCF-7 but not by macrophages. Gene expression profiling showed that though both types of phagocytes expressed full repertoire of the PS recognition and signaling pathway, macrophages could evolve during engulfment of de novo autophagic cells the potential of calreticulin-mediated processes as well. Our data suggest that cells dying through autophagy and those committing anoikis with autophagy may engage in overlapping but distinct sets of clearance mechanisms in professional and non-professional phagocytes.

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Autophagy and signaling: their role in cell survival and cell death

Cited by 1,023 publications

References 89 publications

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

The Pan-Bcl-2 Inhibitor (−)-Gossypol Triggers Autophagic Cell Death in Malignant Glioma

Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes

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