LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: Exploring the Syndecan-Mediated Cellular Internalization of the SARS-CoV-2 Omicron Variant.

Letoha, Annamária / Hudák, Anett / Letoha, Tamás

International journal of molecular sciences

2023 Volume 24, Issue 18

Abstract: SARS-CoV-2 variants evolve to rely more on heparan sulfate (HS) for viral attachment and subsequent infection. In our earlier work, we demonstrated that the Delta variant's spike protein binds more strongly to HS compared to WT SARS-CoV-2, leading to ... ...

Abstract	SARS-CoV-2 variants evolve to rely more on heparan sulfate (HS) for viral attachment and subsequent infection. In our earlier work, we demonstrated that the Delta variant's spike protein binds more strongly to HS compared to WT SARS-CoV-2, leading to enhanced cell internalization via syndecans (SDCs), a family of transmembrane HS proteoglycans (HSPGs) facilitating the cellular entry of the original strain. Using our previously established ACE2- or SDC-overexpressing cellular models, we now compare the ACE2- and SDC-dependent cellular uptake of heat-inactivated WT SARS-CoV-2 with the Delta and Omicron variants. Internalization studies with inactivated virus particles showed that ACE2 overexpression could not compensate for the loss of HS in Omicron's internalization, suggesting that this variant primarily uses HSPGs to enter cells. Although SDCs increased the internalization of all three viruses, subtle differences could be detected between their SDC isoform preferences. The Delta variant particularly benefitted from SDC1, 2, and 4 overexpression for cellular entry, while SDC4 had the most prominent effect on Omicron internalization. The SDC4 knockdown (KD) in Calu-3 cells reduced the cellular uptake of all three viruses, but the inhibition was the most pronounced for Omicron. The polyanionic heparin also hindered the cellular internalization of all three viruses with a dominant inhibitory effect on Omicron. Omicron's predominant HSPG affinity, combined with its preference for the universally expressed SDC4, might account for its efficient transmission yet reduced pathogenicity.
MeSH term(s)	Humans ; Syndecans ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Heparan Sulfate Proteoglycans/genetics ; Heparitin Sulfate ; Extracellular Matrix Proteins
Chemical Substances	Syndecans ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Heparan Sulfate Proteoglycans ; Heparitin Sulfate (9050-30-0) ; Extracellular Matrix Proteins
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241814140
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Article ; Online: Syndecan-3 as a Novel Biomarker in Alzheimer's Disease.

Hudák, Anett / Letoha, Annamária / Vizler, Csaba / Letoha, Tamás

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: Early diagnosis of Alzheimer's disease (AD) is of paramount importance in preserving the patient's mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous ...

Abstract	Early diagnosis of Alzheimer's disease (AD) is of paramount importance in preserving the patient's mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous system (CNS) degeneration in the periphery. Members of the syndecan family of transmembrane proteoglycans are emerging new targets in inflammatory and neurodegenerative disorders. Reviewing the growing scientific evidence on the involvement of syndecans in the pathomechanism of AD, we analyzed the expression of the neuronal syndecan, syndecan-3 (SDC3), in experimental models of neurodegeneration. Initial in vitro studies showed that prolonged treatment of tumor necrosis factor-alpha (TNF-α) increases SDC3 expression in model neuronal and brain microvascular endothelial cell lines. In vivo studies revealed elevated concentrations of TNF-α in the blood and brain of APPSWE-Tau transgenic mice, along with increased SDC3 concentration in the brain and the liver. Primary brain endothelial cells and peripheral blood monocytes isolated from APPSWE-Tau mice exhibited increased SDC3 expression than wild-type controls. SDC3 expression of blood-derived monocytes showed a positive correlation with amyloid plaque load in the brain, demonstrating that SDC3 on monocytes is a good indicator of amyloid pathology in the brain. Given the well-established role of blood tests, the SDC3 expression of monocytes could serve as a novel biomarker for early AD detection.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Biomarkers ; Disease Models, Animal ; Endothelial Cells/metabolism ; Mice ; Mice, Transgenic ; Syndecan-3 ; Syndecans ; Tumor Necrosis Factor-alpha
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Sdc3 protein, mouse ; Syndecan-3 ; Syndecans ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063407
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Syndecan-3 as a Novel Biomarker in Alzheimer’s Disease

Anett Hudák / Annamária Letoha / Csaba Vizler / Tamás Letoha

International Journal of Molecular Sciences, Vol 23, Iss 3407, p

2022 Volume 3407

Abstract: Early diagnosis of Alzheimer’s disease (AD) is of paramount importance in preserving the patient’s mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous ...

Abstract	Early diagnosis of Alzheimer’s disease (AD) is of paramount importance in preserving the patient’s mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous system (CNS) degeneration in the periphery. Members of the syndecan family of transmembrane proteoglycans are emerging new targets in inflammatory and neurodegenerative disorders. Reviewing the growing scientific evidence on the involvement of syndecans in the pathomechanism of AD, we analyzed the expression of the neuronal syndecan, syndecan-3 (SDC3), in experimental models of neurodegeneration. Initial in vitro studies showed that prolonged treatment of tumor necrosis factor-alpha (TNF-α) increases SDC3 expression in model neuronal and brain microvascular endothelial cell lines. In vivo studies revealed elevated concentrations of TNF-α in the blood and brain of APPSWE-Tau transgenic mice, along with increased SDC3 concentration in the brain and the liver. Primary brain endothelial cells and peripheral blood monocytes isolated from APPSWE-Tau mice exhibited increased SDC3 expression than wild-type controls. SDC3 expression of blood-derived monocytes showed a positive correlation with amyloid plaque load in the brain, demonstrating that SDC3 on monocytes is a good indicator of amyloid pathology in the brain. Given the well-established role of blood tests, the SDC3 expression of monocytes could serve as a novel biomarker for early AD detection.
Keywords	Alzheimer’s disease ; biomarkers ; syndecan-3 ; brain ; blood–brain barrier ; blood ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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: Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant's Superior Transmission.

Hudák, Anett / Veres, Gábor / Letoha, Annamária / Szilák, László / Letoha, Tamás

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta's ... ...

Abstract	Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta's spike protein shift the protein towards a net positive electrostatic potential. To understand the key molecular drivers of the Delta infection, we investigate the cellular uptake of the Delta spike protein and Delta spike-bearing SARS-CoV-2 pseudoviruses. Specific in vitro modification of ACE2 and syndecan expression enabled us to demonstrate that syndecan-4, the syndecan isoform abundant in the lung, enhances the transmission of the Delta variant by attaching its mutated spike glycoprotein and facilitating its cellular entry. Compared to the wild-type spike, the Delta one shows a higher affinity towards heparan sulfate proteoglycans than towards ACE2. In addition to attachment to the polyanionic heparan sulfate chains, the Delta spike's molecular interactions with syndecan-4 also involve syndecan-4's cell-binding domain that mediates cell-to-cell adhesion. Regardless of the complexity of these interactions, exogenously added heparin blocks Delta's cellular entry as efficiently as syndecan-4 knockdown. Therefore, a profound understanding of the molecular mechanisms underlying Delta infections enables the development of molecularly targeted yet simple strategies to reduce the Delta variant's spread.
MeSH term(s)	Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/transmission ; Cell Line ; Heparan Sulfate Proteoglycans/antagonists & inhibitors ; Heparan Sulfate Proteoglycans/metabolism ; Humans ; Protein Binding ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; SARS-CoV-2/metabolism ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Syndecan-4/genetics ; Syndecan-4/metabolism ; Virus Internalization
Chemical Substances	Heparan Sulfate Proteoglycans ; Recombinant Proteins ; SDC4 protein, human ; Spike Glycoprotein, Coronavirus ; Syndecan-4 ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23020796
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Contribution of Syndecans to the Cellular Entry of SARS-CoV-2.

Hudák, Anett / Letoha, Annamária / Szilák, László / Letoha, Tamás

International journal of molecular sciences

2021 Volume 22, Issue 10

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here, we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans, facilitate the cellular entry of SARS-CoV-2. Among syndecans, the lung abundant syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus's interactions with syndecans. Besides the polyanionic heparan sulfate chains, other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing the cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offer molecularly precise yet simple strategies to overcome the complex nature of SARS-CoV-2 infection.
MeSH term(s)	Amiloride/pharmacology ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/metabolism ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; COVID-19/metabolism ; COVID-19/virology ; Cell Line ; Cell Survival/drug effects ; Epithelial Sodium Channel Blockers/pharmacology ; Humans ; Peptides/pharmacology ; Protein Domains ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/metabolism ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/metabolism ; Syndecan-4/antagonists & inhibitors ; Syndecan-4/metabolism ; Syndecans/antagonists & inhibitors ; Syndecans/metabolism ; Virus Internalization
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; DX600 peptide ; Epithelial Sodium Channel Blockers ; Peptides ; Receptors, Coronavirus ; SDC4 protein, human ; Spike Glycoprotein, Coronavirus ; Syndecan-4 ; Syndecans ; spike protein, SARS-CoV-2 ; Amiloride (7DZO8EB0Z3) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22105336
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant’s Superior Transmission

Anett Hudák / Gábor Veres / Annamária Letoha / László Szilák / Tamás Letoha

International Journal of Molecular Sciences, Vol 23, Iss 796, p

2022 Volume 796

Abstract	Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta’s spike protein shift the protein towards a net positive electrostatic potential. To understand the key molecular drivers of the Delta infection, we investigate the cellular uptake of the Delta spike protein and Delta spike-bearing SARS-CoV-2 pseudoviruses. Specific in vitro modification of ACE2 and syndecan expression enabled us to demonstrate that syndecan-4, the syndecan isoform abundant in the lung, enhances the transmission of the Delta variant by attaching its mutated spike glycoprotein and facilitating its cellular entry. Compared to the wild-type spike, the Delta one shows a higher affinity towards heparan sulfate proteoglycans than towards ACE2. In addition to attachment to the polyanionic heparan sulfate chains, the Delta spike’s molecular interactions with syndecan-4 also involve syndecan-4’s cell-binding domain that mediates cell-to-cell adhesion. Regardless of the complexity of these interactions, exogenously added heparin blocks Delta’s cellular entry as efficiently as syndecan-4 knockdown. Therefore, a profound understanding of the molecular mechanisms underlying Delta infections enables the development of molecularly targeted yet simple strategies to reduce the Delta variant’s spread.
Keywords	SARS-CoV-2 ; Delta variant ; viral transmission ; cellular entry ; syndecan ; heparan sulfate proteoglycans ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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: Contribution of Syndecans to the Cellular Entry of SARS-CoV-2

Anett Hudák / Annamária Letoha / László Szilák / Tamás Letoha

International Journal of Molecular Sciences, Vol 22, Iss 5336, p

2021 Volume 5336

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here, we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans, facilitate the cellular entry of SARS-CoV-2. Among syndecans, the lung abundant syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus’s interactions with syndecans. Besides the polyanionic heparan sulfate chains, other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing the cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offer molecularly precise yet simple strategies to overcome the complex nature of SARS-CoV-2 infection.
Keywords	coronaviruses ; SARS-CoV-2 ; spike protein ; cellular entry ; syndecans ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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: Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9.

Hudák, Anett / Roach, Matthew / Pusztai, Dávid / Pettkó-Szandtner, Aladár / Letoha, Annamária / Szilák, László / Azzouz, Mimoun / Letoha, Tamás

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene ... ...

Abstract	Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene therapy trials. Among AAVs, AAV9 can translocate through the blood-brain barrier (BBB), making it a promising gene delivery tool for transducing the central nervous system (CNS) via systemic administration. Recent reports on the shortcomings of AAV9-mediated gene delivery into the CNS require reviewing the molecular base of AAV9 cellular biology. A more detailed understanding of AAV9's cellular entry would eradicate current hurdles and enable more efficient AAV9-based gene therapy approaches. Syndecans, the transmembrane family of heparan-sulfate proteoglycans, facilitate the cellular uptake of various viruses and drug delivery systems. Utilizing human cell lines and syndecan-specific cellular assays, we assessed the involvement of syndecans in AAV9's cellular entry. The ubiquitously expressed isoform, syndecan-4 proved its superiority in facilitating AAV9 internalization among syndecans. Introducing syndecan-4 into poorly transducible cell lines enabled robust AAV9-dependent gene transduction, while its knockdown reduced AAV9's cellular entry. Attachment of AAV9 to syndecan-4 is mediated not just by the polyanionic heparan-sulfate chains but also by the cell-binding domain of the extracellular syndecan-4 core protein. Co-immunoprecipitation assays and affinity proteomics also confirmed the role of syndecan-4 in the cellular entry of AAV9. Overall, our findings highlight the universally expressed syndecan-4 as a significant contributor to the cellular internalization of AAV9 and provide a molecular-based, rational explanation for the low gene delivery potential of AAV9 into the CNS.
MeSH term(s)	Humans ; Dependovirus/metabolism ; Heparan Sulfate Proteoglycans ; Heparitin Sulfate/metabolism ; Sulfates ; Syndecan-1 ; Syndecan-4 ; Syndecans/metabolism
Chemical Substances	Heparan Sulfate Proteoglycans ; Heparitin Sulfate (9050-30-0) ; Sulfates ; Syndecan-1 ; Syndecan-4 ; Syndecans ; SDC4 protein, human
Language	English
Publishing date	2023-02-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043141
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology.

Hudák, Anett / Jósvay, Katalin / Domonkos, Ildikó / Letoha, Annamária / Szilák, László / Letoha, Tamás

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer's disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. ...

Abstract	Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer's disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in Aβ pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE-heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated Aβ uptake and aggregation. ApoE2 increased the cellular internalization of monomeric Aβ, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once Aβ aggregated: while ApoE2 reduced the uptake of Aβ aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4's tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of Aβ pathology.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Apolipoprotein E2/metabolism ; Apolipoprotein E4/metabolism ; Apolipoproteins E/metabolism ; Cell Line, Tumor ; Humans ; Protein Aggregates ; Protein Isoforms ; Syndecan-3/metabolism
Chemical Substances	Amyloid beta-Peptides ; ApoE protein, human ; Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E ; Protein Aggregates ; Protein Isoforms ; SDC3 protein, human ; Syndecan-3
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22137070
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology

Anett Hudák / Katalin Jósvay / Ildikó Domonkos / Annamária Letoha / László Szilák / Tamás Letoha

International Journal of Molecular Sciences, Vol 22, Iss 7070, p

2021 Volume 7070

Abstract: Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. ...

Abstract	Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in Aβ pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE–heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated Aβ uptake and aggregation. ApoE2 increased the cellular internalization of monomeric Aβ, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once Aβ aggregated: while ApoE2 reduced the uptake of Aβ aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4′s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of Aβ pathology.
Keywords	ApoE ; amyloid beta ; syndecans ; protein aggregation ; endocytosis ; neurodegeneration ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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.

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED