THSD1

Last update 08 May 2025

Basic Info

Synonyms

thrombospondin type 1 domain containing 1, Thrombospondin type-1 domain-containing protein 1, THSD1

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Introduction

Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.

100 Clinical Results associated with THSD1

100 Translational Medicine associated with THSD1

0 Patents (Medical) associated with THSD1

229

Literatures (Medical) associated with THSD1

04 Apr 2025·Medicine

Mendelian randomization analysis of the causal relationship between plasma proteins and childhood asthma

Article

Author: Sun, Liping ; Fan, Hui ; Wang, Caiwen ; Sun, Yingying

Existing studies have suggested a significant association between plasma proteins and childhood asthma, but the specific causal relationship between them remains unclear. Therefore, we aimed to evaluate the causal relationship between plasma proteins and childhood asthma using Mendelian randomization (MR) methods. We conducted a 2-sample MR analysis and a reverse MR analysis. The GWAS summary statistics for plasma proteins were derived from a European population, covering a total of 4907 plasma proteins. The GWAS summary statistics for childhood asthma were obtained from the FinnGen database, including 3025 childhood asthma patients and 135,449 normal controls. Five MR methods, which include inverse-variance weighted, weighted median, MR-Egger, weighted mode, and simple mode, were utilized to investigate the causal relationship between plasma proteins and childhood asthma. The results indicated that ITIH4 is a risk factor for childhood asthma, while THSD1, AMIGO2, L1CAM, MICB, and SELE are protective factors. Leave-one-out analysis, heterogeneity tests, and pleiotropy tests confirmed the reliability and robustness of our findings. Additionally, reverse MR analysis showed no significant causal relationship between childhood asthma and ITIH4, THSD1, AMIGO2, L1CAM, MICB, and SELE. Our study used MR methods to confirm the specific causal relationships between 4907 plasma proteins and childhood asthma. Specifically, ITIH4 was likely to be significantly associated with an increased risk of childhood asthma, while THSD1, AMIGO2, L1CAM, MICB, and SELE were likely to be significantly associated with a reduced risk of childhood asthma.

01 Apr 2025·Nature Chemical Biology

FUT10 and FUT11 are protein O-fucosyltransferases that modify protein EMI domains

Article

Author: Hao, Huilin ; Neely, G Gregory ; Moreno, Cesar L ; Norris, Nicholas ; Cielesh, Michelle ; Ito, Atsuko ; Payne, Richard J ; Tjondro, Harry ; Haltiwanger, Robert S ; Urbauer, Ramona J Bieber ; Passam, Freda H ; Kebede, Melkam A ; Larance, Mark ; Yuan, Youxi ; Eberand, Benjamin M ; Maxwell, Joshua W C

AbstractO-Fucosylation plays crucial roles in various essential biological events. Alongside the well-established O-fucosylation of epidermal growth factor-like repeats by protein O-fucosyltransferase 1 (POFUT1) and thrombospondin type 1 repeats by POFUT2, we recently identified a type of O-fucosylation on the elastin microfibril interface (EMI) domain of Multimerin-1 (MMRN1). Here, using AlphaFold2 screens, co-immunoprecipitation, enzymatic assays combined with mass spectrometric analysis and CRISPR–Cas9 knockouts, we demonstrate that FUT10 and FUT11, originally annotated in UniProt as α1,3-fucosyltransferases, are actually POFUTs responsible for modifying EMI domains; thus, we renamed them as POFUT3 and POFUT4, respectively. Like POFUT1/2, POFUT3/4 function in the endoplasmic reticulum, require folded domain structures for modification and participate in a non-canonical endoplasmic reticulum quality control pathway for EMI domain-containing protein secretion. This finding expands the O-fucosylation repertoire and provides an entry point for further exploration in this emerging field of O-fucosylation.

01 Feb 2025·Neurology and Therapy

Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study

Article

Author: Marie, Sébastien ; Godfrin, Yann ; Lemarchant, Sighild ; Pasculli, Giuseppe ; Kremer, Philip ; Le Douce, Juliette ; Janus, Annette ; Bambury, Pauline ; Dumas, Daniël

INTRODUCTIONBlood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells. NX210c demonstrated a good safety profile in a single ascending dose phase 1a clinical study. The present multiple ascending dose phase 1b study was performed to evaluate the tolerability and pharmacological effects of repeated doses of NX210c in healthy elderly (age: > 55 years) volunteers.METHODSThis was a randomized, placebo-controlled, double-blind study (EudraCT No. 2022-002868-76), investigating safety/tolerability, pharmacokinetics, and pharmacodynamics (including blood and cerebrospinal fluid biomarkers). Participants received 5 or 10 mg/kg NX210c or placebo (10-min infusion) thrice weekly for 4 weeks in an ascending dose fashion. Follow-up was conducted 2 weeks after last dosing.RESULTSThe investigation included 29 participants. No serious adverse events were recorded and all adverse events were mild. Dedicated central nervous system testing did not reveal neurotoxicity. Biomarker evaluation showed a statistically significant reduction in blood claudin-5 and a trend toward reduction of blood homocysteine. In silico data modelling revealed salient pharmacokinetic-pharmacodynamic relationships, including reduction of claudin-5, neurofilament light chain, and SPARC-like protein 1 release, and degradation of homocysteine.CONCLUSIONMultiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available.

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THSD1

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