LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: Autophagy induction in the treatment of Alzheimer's disease.

Schmukler, Eran / Pinkas-Kramarski, Ronit

2019 Volume 81, Issue 2, Page(s) 184–193

Abstract: A growing body of evidence indicates that autophagy, an intracellular degradation pathway, profoundly affects Alzheimer's disease (AD) pathogenesis. Autophagy mediates the degradation of neurotoxic material and damaged organelles, allowing their ... ...

Abstract	A growing body of evidence indicates that autophagy, an intracellular degradation pathway, profoundly affects Alzheimer's disease (AD) pathogenesis. Autophagy mediates the degradation of neurotoxic material and damaged organelles, allowing their clearance by glial and neuronal cells, while impaired autophagy may account for the accumulation of protein aggregates. Accordingly, dysfunctional autophagy is one of AD hallmarks; it occurs early in the disease development, which makes it an attractive therapeutic intervention target. Therefore, in recent years, the potential of autophagy induction as a treatment for AD has been studied extensively using various autophagy inducers, most of which are already in clinical practice for other medical conditions. Albeit promising results, including in AD clinical trials, this therapeutic strategy still requires careful consideration in order to fully understand the role of autophagy in AD pathogenesis and to further improve the outcomes. This review summarizes the current findings in this field and raises open questions and new prospects.
Language	English
Publishing date	2019-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604587-x
ISSN	1098-2299 ; 0272-4391
ISSN (online)	1098-2299
ISSN	0272-4391
DOI	10.1002/ddr.21605
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.B 2542: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article: Autophagy is induced and modulated by cholesterol depletion through transcription of autophagy-related genes and attenuation of flux.

Shapira, Keren E / Shapira, Guy / Schmukler, Eran / Pasmanik-Chor, Metsada / Shomron, Noam / Pinkas-Kramarski, Ronit / Henis, Yoav I / Ehrlich, Marcelo

Cell death discovery

2021 Volume 7, Issue 1, Page(s) 320

Abstract: Perturbations to cellular homeostasis, including reduction of the cholesterol level, induce autophagy, a self-digestion process of cellular constituents through an autophagosomal-lysosomal pathway. In accord with its function as a membrane organizer and ... ...

Abstract	Perturbations to cellular homeostasis, including reduction of the cholesterol level, induce autophagy, a self-digestion process of cellular constituents through an autophagosomal-lysosomal pathway. In accord with its function as a membrane organizer and metabolic sentinel, the cellular response to cholesterol depletion comprises multiple phenomena, including the activation of transcriptional responses, accumulation of reactive oxygen species (ROS), and activation of stress-related signaling pathways. However, the molecular mechanisms by which cholesterol depletion regulates autophagy and the putative involvement of transcriptional responses, ROS and/or stress-related signaling in autophagy regulation in this biological context are not fully understood. Here, we find that cholesterol depletion regulates autophagy at three different levels. First, employing RNA-seq, we show that cholesterol depletion increases the expression of autophagy-related genes independent of ROS or JNK activity. Second, analysis of LC3 lipidation and intracellular localization, and of p62 levels and degradation kinetics, reveals that cholesterol depletion mediates autophagy induction while interfering with autophagic flux. Of note, only the latter depends on ROS accumulation and JNK activity. In view of the common use of cholesterol-reducing drugs as therapeutic agents, our findings have important implications for multiple cellular settings in which autophagy plays a prominent role.
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-021-00718-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Effects of APOE4 on Mitochondrial Dynamics and Proteins in vivo.

Simonovitch, Shira / Schmukler, Eran / Masliah, Eliezer / Pinkas-Kramarski, Ronit / Michaelson, Daniel M

Journal of Alzheimer's disease : JAD

2019 Volume 70, Issue 3, Page(s) 861–875

Abstract: This study examined the effects of apolipoprotein E4 (APOE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), on proteins involved in mitochondrial dynamics and autophagy, in the hippocampus of targeted replacement mice. ... ...

Abstract	This study examined the effects of apolipoprotein E4 (APOE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), on proteins involved in mitochondrial dynamics and autophagy, in the hippocampus of targeted replacement mice. Immunohistochemical measurements revealed that the levels of the mitochondrial fusion-mediating protein, MFN1, were higher, whereas those of corresponding fission-regulating protein, DRP-1, were lower in the hippocampus of ApoE4 mice than in the corresponding ApoE3 mice, indicating that APOE4 is associated with increased mitochondrial fusion and decreased fission. A similar ApoE4-driven decrease in DRP-1 was also observed in AD brains. The levels of the mitochondrial proteins COX1 and Tom40, were higher in the ApoE4 mice, which is consistent with the increased fusion. Measurements of the levels of cleaved PINK1 and parkin, which mark and target mitochondria for mitophagic degradation, revealed lower levels of cleaved PINK1, suggesting reduced mitochondrial membrane potential, and higher levels of parkin in the hippocampus of ApoE4 compared with the ApoE3 mice, indicating altered mitophagy. The levels of the ubiquitin-binding scaffold protein, p62/SQSTM1, which directs selected cargo to the autophagosomes, were also higher in the ApoE4 mice. These findings suggest that APOE4 is associated with enhanced mitochondrial fusion and decreased fission. Additionally, the results indicate that mitophagy/autophagy is reduced in ApoE4 mice, resulting in higher levels of proteins such as parkin and p62, which are normally degraded during this process. Taken together, these results suggest a novel mechanism that may underlie the pathological effects of APOE4 and indicate that use of APOE4 genotyping could pave the way for identification of novel APOE4-related therapeutic targets.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Animals ; Apolipoprotein E3/genetics ; Apolipoprotein E3/metabolism ; Apolipoprotein E4/genetics ; Apolipoprotein E4/metabolism ; Autophagy/physiology ; Hippocampus/metabolism ; Immunohistochemistry ; Mice ; Mitochondrial Dynamics/physiology ; Mitochondrial Proteins/metabolism ; Mitophagy/physiology ; Neurons/metabolism ; Protein Kinases/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Apolipoprotein E3 ; Apolipoprotein E4 ; Mitochondrial Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-) ; PTEN-induced putative kinase (EC 2.7.11.1)
Language	English
Publishing date	2019-07-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-190074
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6084: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Altered mitochondrial dynamics and function in APOE4-expressing astrocytes.

Schmukler, Eran / Solomon, Shira / Simonovitch, Shira / Goldshmit, Yona / Wolfson, Eya / Michaelson, Daniel Morris / Pinkas-Kramarski, Ronit

Cell death & disease

2020 Volume 11, Issue 7, Page(s) 578

Abstract: APOE4 is a major risk factor for sporadic Alzheimer's disease; however, it is unclear how it exerts its pathological effects. Others and we have previously shown that autophagy is impaired in APOE4 compared to APOE3 astrocytes, and demonstrated ... ...

Abstract	APOE4 is a major risk factor for sporadic Alzheimer's disease; however, it is unclear how it exerts its pathological effects. Others and we have previously shown that autophagy is impaired in APOE4 compared to APOE3 astrocytes, and demonstrated differences in the expression of mitochondrial dynamics proteins in brains of APOE3 and APOE4 transgenic mice. Here, we investigated the effect of APOE4 expression on several aspects of mitochondrial function and network dynamics, including fusion, fission, and mitophagy, specifically in astrocytes. We found that APOE3 and APOE4 astrocytes differ in their mitochondrial dynamics, suggesting that the mitochondria of APOE4 astrocytes exhibit reduced fission and mitophagy. APOE4 astrocytes also show impaired mitochondrial function. Importantly, the autophagy inducer rapamycin enhanced mitophagy and improved mitochondrial functioning in APOE4 astrocytes. Collectively, the results demonstrate that APOE4 expression is associated with altered mitochondrial dynamics, which might lead to impaired mitochondrial function in astrocytes. This, in turn, may contribute to the pathological effects of APOE4 in Alzheimer's disease.
MeSH term(s)	Apolipoprotein E3/metabolism ; Apolipoprotein E4/metabolism ; Astrocytes/metabolism ; Astrocytes/ultrastructure ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Cell Line ; Humans ; Lysosomes/drug effects ; Lysosomes/metabolism ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Mitochondrial Dynamics ; Mitochondrial Proteins/metabolism ; Proteasome Endopeptidase Complex/drug effects ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis/drug effects ; Sirolimus/pharmacology ; Ubiquitination/drug effects
Chemical Substances	Apolipoprotein E3 ; Apolipoprotein E4 ; Mitochondrial Proteins ; Carbonyl Cyanide m-Chlorophenyl Hydrazone (555-60-2) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2020-07-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-020-02776-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Nucleolin and ErbB2 inhibition reduces tumorigenicity of ErbB2-positive breast cancer.

Wolfson, Eya / Solomon, Shira / Schmukler, Eran / Goldshmit, Yona / Pinkas-Kramarski, Ronit

Cell death & disease

2018 Volume 9, Issue 2, Page(s) 47

Abstract: ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives ... ...

Abstract	ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients. Given these results, and since acquired resistance to anti-ErbB2-targeted therapy is a major obstacle in treatment of breast cancer, we have examined the therapeutic potential of targeting the ErbB2-nucleolin complex. The effect of the nucleolin-specific inhibitor GroA (AS1411) on ErbB2-positive breast cancer was tested in vivo, in a mouse xenograft model for breast cancer; as well as in vitro, alone and in combination with the ErbB2 kinase-inhibitor tyrphostin AG-825. Here, we show that in vivo treatment of ErbB2-positive breast tumor xenografts with GroA reduces tumor size and leads to decreased ErbB2-mediated signaling. Moreover, we found that co-treatment of breast cancer cell lines with GroA and the ErbB2 kinase-inhibitor tyrphostin AG-825 enhances the anti-cancer effects exerted by GroA alone in terms of cell viability, mortality, migration, and invasiveness. We, therefore, suggest a novel therapeutic approach, consisting of combined inhibition of ErbB2 and nucleolin, which has the potential to improve breast cancer treatment efficacy.
MeSH term(s)	Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Aptamers, Nucleotide ; Benzothiazoles/administration & dosage ; Benzothiazoles/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Oligodeoxyribonucleotides/administration & dosage ; Oligodeoxyribonucleotides/pharmacology ; Phosphoproteins/antagonists & inhibitors ; Phosphoproteins/metabolism ; RNA-Binding Proteins/antagonists & inhibitors ; RNA-Binding Proteins/metabolism ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/metabolism ; Signal Transduction ; Tyrphostins/administration & dosage ; Tyrphostins/pharmacology ; Xenograft Model Antitumor Assays ; Nucleolin
Chemical Substances	AGRO 100 ; Aptamers, Nucleotide ; Benzothiazoles ; Oligodeoxyribonucleotides ; Phosphoproteins ; RNA-Binding Proteins ; Tyrphostins ; tyrphostin AG825 ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2018-01-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-017-0067-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Blood Glutamate Scavenger as a Novel Neuroprotective Treatment in Spinal Cord Injury.

Goldshmit, Yona / Jona, Ghil / Schmukler, Eran / Solomon, Shira / Pinkas-Kramarski, Ronit / Ruban, Angela

Journal of neurotrauma

2018 Volume 35, Issue 21, Page(s) 2581–2590

Abstract: Neurotrauma causes immediate elevation of extracellular glutamate (Glu) levels, which creates excitotoxicity and facilitates inflammation, glial scar formation, and consequently neuronal death. Finding factors that reduce the inflammatory response and ... ...

Abstract	Neurotrauma causes immediate elevation of extracellular glutamate (Glu) levels, which creates excitotoxicity and facilitates inflammation, glial scar formation, and consequently neuronal death. Finding factors that reduce the inflammatory response and glial scar formation, and increase neuronal survival and neurite outgrowth, are of major importance for improving the outcome after spinal cord injury (SCI). In the present study, we evaluated a new treatment aiming to remove central nervous system (CNS) Glu into the systemic blood circulation by intravenous (IV) administration of blood Glu scavengers (BGS) such as the enzyme recombinant glutamate-oxaloacetate transaminase 1 (rGOT1) and its co-substrate. In this study we induced in mice an SCI (hemisection), and 1 h post-injury started administering BGS treatment for 5 consecutive days. The treatment reduced the expression levels of p-p38, which regulates apoptosis and increased the expression of p-Akt, which mediates cell survival. Moreover, this treatment decreased pro-inflammatory cytokine expression and microglia activation, reduced astrocytes' reactivity, and facilitated expression of radial glia markers such as Pax6 and nestin. BGS treatment increased the survival of neurons at lesion site and enabled axonal regeneration into the injury site. These effects were correlated with improved functional recovery of the left paretic hindlimb. Thus, early pharmacological intervention with BGS following SCI may be neuroprotective and create a pro-regenerative environment by modulating glia cell response. In light of our results, the availability of the method to remove excess Glu from CNS without the need to deliver drugs across the blood-brain barrier (BBB) and with minimal or no adverse effects may provide a major therapeutic asset.
MeSH term(s)	Animals ; Aspartate Aminotransferase, Cytoplasmic/pharmacology ; Female ; Glutamic Acid/blood ; Glutamic Acid/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Recombinant Proteins/pharmacology ; Spinal Cord Injuries/blood
Chemical Substances	Neuroprotective Agents ; Recombinant Proteins ; Glutamic Acid (3KX376GY7L) ; Aspartate Aminotransferase, Cytoplasmic (EC 2.6.1.-)
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2017.5524
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2016: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Ras and autophagy in cancer development and therapy.

Schmukler, Eran / Kloog, Yoel / Pinkas-Kramarski, Ronit

Oncotarget

2014 Volume 5, Issue 3, Page(s) 577–586

Abstract: Autophagy, a process of self-degradation and turnover of cellular components, plays a complex role in cancer. Evidence exists to show that autophagy may support tumor growth and cell survival, whereas it can also contribute to tumor suppression and have ... ...

Abstract	Autophagy, a process of self-degradation and turnover of cellular components, plays a complex role in cancer. Evidence exists to show that autophagy may support tumor growth and cell survival, whereas it can also contribute to tumor suppression and have anti-survival characteristics in different cellular systems. Numerous studies have described the effects of various oncogenes and tumor suppressors on autophagy. The small GTPase Ras is an oncogene involved in the regulation of various cell-signaling pathways, and is mutated in 33% of human cancers. In the present review, we discuss the interplay between Ras and autophagy in relation to oncogenesis. It appears that Ras can upregulate or downregulate autophagy through several signaling pathways. In turn, autophagy can affect the tumorigenicity driven by Ras, resulting in either tumor progression or repression, depending on the cellular context. Furthermore, Ras inhibitors were shown to induce autophagy in several cancer cell lines.
MeSH term(s)	Animals ; Autophagy/genetics ; Cell Transformation, Neoplastic/genetics ; Genes, ras ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Signal Transduction
Language	English
Publishing date	2014-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.1775
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Continuous treatment with FTS confers resistance to apoptosis and affects autophagy.

Schmukler, Eran / Wolfson, Eya / Elazar, Zvulun / Kloog, Yoel / Pinkas-Kramarski, Ronit

PloS one

2017 Volume 12, Issue 2, Page(s) e0171351

Abstract: High percentage of human cancers involves alteration or mutation in Ras proteins, including the most aggressive malignancies, such as lung, colon and pancreatic cancers. FTS (Salirasib) is a farnesylcysteine mimetic, which acts as a functional Ras ... ...

Abstract	High percentage of human cancers involves alteration or mutation in Ras proteins, including the most aggressive malignancies, such as lung, colon and pancreatic cancers. FTS (Salirasib) is a farnesylcysteine mimetic, which acts as a functional Ras inhibitor, and was shown to exert anti-tumorigenic effects in vitro and in vivo. Previously, we have demonstrated that short-term treatment with FTS also induces protective autophagy in several cancer cell lines. Drug resistance is frequently observed in cancer cells exposed to prolonged treatment, and is considered a major cause for therapy inefficiency. Therefore, in the present study, we examined the effect of a prolonged treatment with FTS on drug resistance of HCT-116 human colon cancer cells, and the involvement of autophagy in this process. We found that cells grown in the presence of FTS for 6 months have become resistant to FTS-induced cell growth inhibition and cell death. Furthermore, we discovered that the resistant cells exhibit altered autophagy, reduced apoptosis and changes in Ras-related signaling pathways following treatment with FTS. Moreover we found that while FTS induces an apoptosis-related cleavage of p62, the FTS-resistant cells were more resistant to apoptosis and p62 cleavage.
MeSH term(s)	Apoptosis/drug effects ; Autophagy/drug effects ; Cell Death/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm ; Farnesol/analogs & derivatives ; Farnesol/pharmacology ; Genes, ras/drug effects ; HCT116 Cells/drug effects ; Humans ; Real-Time Polymerase Chain Reaction ; Salicylates/pharmacology ; Signal Transduction/drug effects
Chemical Substances	Salicylates ; farnesylthiosalicylic acid ; Farnesol (4602-84-0)
Language	English
Publishing date	2017-02-02
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0171351
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: DJ-1 deficiency impairs autophagy and reduces alpha-synuclein phagocytosis by microglia.

Nash, Yuval / Schmukler, Eran / Trudler, Dorit / Pinkas-Kramarski, Ronit / Frenkel, Dan

Journal of neurochemistry

2017 Volume 143, Issue 5, Page(s) 584–594

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder, of which 1% of the hereditary cases are linked to mutations in DJ-1, an oxidative stress sensor. The pathological hallmark of PD is intercellular inclusions termed Lewy Bodies, ... ...

Abstract	Parkinson's disease (PD) is a progressive neurodegenerative disorder, of which 1% of the hereditary cases are linked to mutations in DJ-1, an oxidative stress sensor. The pathological hallmark of PD is intercellular inclusions termed Lewy Bodies, composed mainly of α-Synuclein (α-Syn) protein. Recent findings have shown that α-Syn can be transmitted from cell to cell, suggesting an important role of microglia, as the main scavenger cells of the brain, in clearing α-Syn. We previously reported that the knock down (KD) of DJ-1 in microglia increased cells' neurotoxicity to dopaminergic neurons. Here, we discovered that α-Syn significantly induced elevated secretion of the proinflammatory cytokines IL-6 and IL-1β and a significant dose-dependent elevation in the production of nitric oxide in DJ-1 KD microglia, compared to control microglia. We further investigated the ability of DJ-1 KD microglia to uptake and degrade soluble α-Syn, and discovered that DJ-1 KD reduces cell-surface lipid raft expression in microglia and impairs their ability to uptake soluble α-Syn. Autophagy is an important mechanism for degradation of intracellular proteins and organelles. We discovered that DJ-1 KD microglia exhibit an impaired autophagy-dependent degradation of p62 and LC3 proteins, and that manipulation of autophagy had less effect on α-Syn uptake and clearance in DJ-1 KD microglia, compared to control microglia. Further studies of the link between DJ-1, α-Syn uptake and autophagy may provide useful insights into the role of microglia in the etiology of the PD.
MeSH term(s)	Animals ; Autophagy/drug effects ; Cells, Cultured ; Cytokines/metabolism ; Dopaminergic Neurons/drug effects ; Humans ; Mice, Inbred BALB C ; Microglia/drug effects ; Oxidative Stress/drug effects ; Phagocytosis/drug effects ; Protein Deglycase DJ-1/deficiency ; Protein Deglycase DJ-1/metabolism ; alpha-Synuclein/metabolism ; alpha-Synuclein/pharmacology
Chemical Substances	Cytokines ; alpha-Synuclein ; Protein Deglycase DJ-1 (EC 3.1.2.-)
Language	English
Publishing date	2017-10-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.14222
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.170: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Enhancing FTS (Salirasib) efficiency via combinatorial treatment.

Wolfson, Eya / Schmukler, Eran / Schokoroy, Sari Trangle / Kloog, Yoel / Pinkas-Kramarski, Ronit

Biology of the cell

2015 Volume 107, Issue 5, Page(s) 130–143

Abstract: The Ras oncogene transmits signals, which regulate various cellular processes including cell motility, differentiation, growth and death. Since Ras signalling is abnormally activated in more than 30% of human cancers, Ras and its downstream signalling ... ...

Abstract	The Ras oncogene transmits signals, which regulate various cellular processes including cell motility, differentiation, growth and death. Since Ras signalling is abnormally activated in more than 30% of human cancers, Ras and its downstream signalling pathways are considered good targets for therapeutic interference. Ras is post-translationally modified by the addition of a farnesyl group, which permits its attachment to the plasma membrane. Exploiting this knowledge, a synthetic Ras inhibitor, S-trans, trans-farnesylthiosalicylic acid (FTS; Salirasib), was developed. FTS resembles the farnesylcysteine group of Ras, and acts as an effective Ras antagonist. In the present review, the effect of FTS in combination with various other drugs, as tested in vitro and in vivo, and its therapeutic potential are discussed. As reviewed, FTS cooperates with diverse therapeutic agents, which significantly improves treatment outcome. Therefore, combinations of FTS with other agents have a potential to serve as anti-cancer or anti-inflammatory therapies.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Farnesol/analogs & derivatives ; Farnesol/pharmacology ; Humans ; Neoplasms/drug therapy ; Salicylates/pharmacology ; Signal Transduction/drug effects
Chemical Substances	Anti-Inflammatory Agents ; Antineoplastic Agents ; Salicylates ; farnesylthiosalicylic acid ; Farnesol (4602-84-0)
Language	English
Publishing date	2015-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1111/boc.201400087
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 758: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito