Last update 19 Sep 2024

Siglec-9

Last update 19 Sep 2024

Basic Info

Synonyms

CD329, CDw329, Protein FOAP-9

+ [4]

Introduction

Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.

Drugs associated with Siglec-9

IPH26

Target

Siglec-9

Mechanism

Siglec-9 modulators

Active Org.-

Originator Org.

Innate Pharma SA

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HG-1230

Target

Siglec-7 x Siglec-9

Mechanism

Siglec-7 modulators [+1]

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Immune System Diseases [+2]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Siglec-9

100 Translational Medicine associated with Siglec-9

0 Patents (Medical) associated with Siglec-9

208

Literatures (Medical) associated with Siglec-9

01 Oct 2024·Experimental Gerontology

Identification of potential drug targets for amyotrophic lateral sclerosis by Mendelian randomization analysis based on brain and plasma proteomics

Article

Author: Xu, Pengfei ; Qi, Xianghua ; Yang, Ni ; Ren, Fang ; Shi, Liangyuan ; Li, Chunlin

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.

14 Aug 2024·mBio

Neisserial adhesin A (NadA) binds human Siglec-5 and Siglec-14 with high affinity and promotes bacterial adhesion/invasion

Article

Author: Calvaresi, Valeria ; Giordano, Anna ; Viviani, Viola ; Faleri, Agnese ; Norais, Nathalie ; Rappuoli, Rino ; d'Alterio, Liana ; Maione, Domenico ; Bartolini, Erika ; Sampieri, Katia ; Pansegrau, Werner ; Pinzuti, Irene ; Benucci, Barbara ; Utrio Lanfaloni, Sabrina ; Merola, Marcello ; Masignani, Vega ; Spinello, Zaira ; Pizza, Mariagrazia ; Perrotta, Andrea

ABSTRACT Neisserial adhesin A (NadA) is a meningococcal surface protein included as recombinant antigen in 4CMenB, a protein-based vaccine able to induce protective immune responses against Neisseria meningitidis serogroup B (MenB). Although NadA is involved in the adhesion/invasion of epithelial cells and human myeloid cells, its function in meningococcal physiology is still poorly understood. To clarify the role played by NadA in the host-pathogen interaction, we sought to identify its cellular receptors. We screened a protein microarray encompassing 2,846 human and 297 mouse surface/secreted recombinant proteins using recombinant NadA as probe. Efficient NadA binding was revealed on the paired sialic acid-binding immunoglobulin-type lectins receptors 5 and 14 (Siglec-5 and Siglec-14), but not on Siglec-9 therein used as control. The interaction was confirmed by biochemical tools with the determination of the KD value in the order of nanomolar and the identification of the NadA binding site by hydrogen-deuterium exchange coupled to mass spectrometry. The N-terminal domain of the Siglec-5 that recognizes the sialic acid was identified as the NadA binding domain. Intriguingly, exogenously added recombinant soluble Siglecs, including Siglec-9, were found to decorate N. meningitidis surface in a NadA-dependent manner. However, Siglec-5 and Siglec-14 transiently expressed in CHO-K1 cells endorsed NadA binding and increased N. meningitidis adhesion/invasion while Siglec-9 did not. Taken together, Siglec-5 and Siglec-14 satisfy all features of NadA receptors suggesting a possible role of NadA in the acute meningococcal infection. IMPORTANCE Bacteria have developed several strategies for cell colonization and immune evasion. Knowledge of the host and pathogen factors involved in these mechanisms is crucial to build efficacious countermoves. Neisserial adhesin A (NadA) is a meningococcal surface protein included in the anti-meningococcus B vaccine 4CMenB, which mediates adhesion to and invasion of epithelial cells. Although NadA has been shown to bind to other cell types, like myeloid and endothelial cells, it still remains orphan of a defined host receptor. We have identified two strong NadA interactors, Siglec-5 and Siglec-14, which are mainly expressed on myeloid cells. This showcases that NadA is an additional and key player among the Neisseria meningitidis factors targeting immune cells. We thus provide novel insights on the strategies exploited by N. meningitidis during the infection process, which can progress to a severe illness and death.

01 May 2024·Cytokine

Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD

Article

Author: Ge, Linyang ; Zhou, Linfu ; Chen, Zi ; Xu, Shuanglan ; Wang, Nan

BACKGROUNDThe pathogenesis and treatment strategies for chronic obstructive pulmonary disease (COPD) require further exploration. Abnormal neutrophil inflammation and the overexpression of neutrophil extracellular traps (NETs) are closely associated with acute exacerbations of COPD (AECOPD). Siglec-9, a specific receptor expressed on neutrophils that inhibits their function, prompted us to investigate its relationship with NETs found in induced sputum and the severity of the disease.METHODSWe collected clinical data from patients with AECOPD and assessed the expression of Siglec-9 in peripheral blood neutrophils and the presence of NETs in induced sputum. We then observed the correlation between Siglec-9, the inflammatory response, and the severity of AECOPD.RESULTSWe observed an increase in the expression of Siglec-9 in the peripheral blood neutrophils of patients with AECOPD. Concurrently, these patients exhibited more severe clinical symptoms, higher systemic inflammation levels, and a reduced quality of life compared to those with induced sputum NET expression. Further subgroup analysis of AECOPD patients with high Siglec-9 expression revealed worsened quality of life and more severe inflammation, particularly in indicators such as the BODE index, CRP, peripheral blood neutrophil count, IL-6, IL-8, TNF-α expression, and others. Furthermore, we noted a significant increase in NET-specific expression in the sputum of patients with high Siglec-9 expression levels. In comparison to patients with low Siglec-9 expression, those with high expression experienced more systemic inflammatory reactions and a lower quality of life. Correlation analysis of the aforementioned indicators revealed that the expression ratio of Siglec-9 in the peripheral blood of patients correlated with lung function, quality of life, and NETs in the induced sputum of patients with AECOPD.CONCLUSIONThe increased expression of Siglec-9 in peripheral blood neutrophils of AECOPD patients leads to elevated NET expression in induced sputum, exacerbating the systemic inflammatory response and worsening lung function and quality of life in these patients.

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Siglec-9

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