Netrin‐1 and multiple sclerosis: a new biomarker for neuroinflammation?

Mulero, Patricia; Cordova, Claudia; Hernández, Marita; Martín, Rubén; Gutiérrez, Beatriz; Muñoz, Juan Carlos; Redondo, Noemí; Gallardo, Isabel; Téllez, Nieves; Nieto, Marı́a Luisa

doi:10.1111/ene.13340

Cited by 30 publications

(25 citation statements)

References 24 publications

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“…Furthermore, neutralization of UNC5B receptor‐induced monocyte and neutrophil infiltration thus increased kidney injury . In line with these results, obese patients and patients with multiple sclerosis showed significantly lower circulating Netrin‐1 levels than those of controls. Liu, et al reported that plasma Netrin‐1 levels were lower in newly diagnosed type 2 diabetes mellitus patients than those in healthy controls and also the levels were negatively correlated with blood glucose levels and insulin resistance.…”

Section: Discussionsupporting

confidence: 73%

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Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Günpınar

Meraci

Dündar

2019

J of Periodontal Research

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Objectives The aim of this present study was to evaluate the levels of Netrin‐1 and Unc5b in periodontal health and disease. Background Netrin‐1, acting via its receptor UNC5b, regulates the inflammatory response and takes apart in bone destructive diseases. Methods Samples of gingival crevicular fluid (GCF), whole saliva, and serum were taken from systemically healthy, nonsmoking 20 periodontitis , 20 gingivitis patients, and 20 periodontally healthy subjects at baseline and 4 weeks after nonsurgical periodontal treatment (NSPT). Whole‐mouth and site‐specific clinical periodontal parameters were recorded. Netrin‐1 and Unc5b levels were measured by enzyme‐linked immunosorbent assay. Data were analyzed by nonparametric tests. Results Total amount of Netrin‐1 in GCF was significantly higher in periodontitis than the others, and the levels were significantly reduced after NSPT. Salivary and serum concentrations of Netrin‐1 were significantly different among the study groups (P = .000), and NSPT significantly increased the concentration levels of both salivary and serum Netrin‐1 (P < .05). Healthy subjects had significantly lower GCF (P = .001) and conversely, higher salivary and serum levels of Unc5b than the other groups (P = .002). The GCF levels of Unc5b were significantly reduced (P < .01), and conversely, serum concentrations were significantly increased after NSPT (P < .05). GCF Netrin‐1 and Unc5b total amounts were positively correlated with clinical parameters (P < .01 and P < .05) whereas salivary Netrin‐1 and Unc5b concentrations were negatively correlated with clinical parameters (P < .01 and P < .05). Conclusions The results of this study indicate that Netrin‐1 and its receptor Unc5b may have essential roles in periodontal inflammation and those can be assumed as useful therapeutic agent to control inflammation and periodontal breakdown.

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Section: Discussionsupporting

confidence: 73%

“…Furthermore, neutralization of UNC5B receptor-induced monocyte and neutrophil infiltration thus increased kidney injury. 12 In line with these results, obese patients 15 and patients with multiple sclerosis 30 showed significantly lower circulating Netrin-1 levels than those of controls. Liu, et al 31 reported…”

Section: Discussionsupporting

confidence: 65%

Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Günpınar

Meraci

Dündar

2019

J of Periodontal Research

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“…In the present study, TNFα, a proinflammatory marker has been shown to increase in RR-multiple sclerosis [75,76] and to be consistently elevated regardless of the status of disease type (i.e., clinically isolated syndrome, primary progressive, or relapsing-remitting), with serum levels 40-50% higher in multiple sclerosis subjects relative to controls. Preclinical studies have reported an association between TNFα and impaired memory in mice with EAE [77] and implicated astrocyte signaling as the downstream target of overexpression of the cytokine.…”

Section: Discussion and Summarysupporting

confidence: 52%

Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

Patel¹,

Zagon²,

Thomas³

et al. 2020

An Overview and Management of Multiple Chronic Conditions

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Multiple sclerosis (MS) is accompanied by decreases in serum endogenous enkephalin/endorphins and alterations in inflammatory cytokines. This retrospective analysis of serum levels was conducted in 53 patients with established relapsing-remitting MS treated with the disease-modifying therapies (DMT) glatiramer acetate, dimethyl fumarate or with the biotherapeutic low dose naltrexone (LDN) to elevate enkephalins, an off-label alternative. Opioid growth factor (OGF), an inhibitory endogenous opioid involved in modulating cellular replication, was measured and correlated to serum β-endorphin, IL-17A and TNFα. Results revealed that MS leads to a significant reduction in OGF levels in subjects on DMTs, but patients on LDN had OGF levels comparable to non-MS controls. Individuals on DMTs had significantly elevated TNFα levels, while IL-17A levels were significantly elevated only in patients taking dimethyl fumarate. A direct correlation was established between OGF and IL17A indicating a potential interaction between the OGF-OGFr axis and pro-inflammatory T-helper cells providing insight into the disease etiology.

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“…The management and outcome of multiple sclerosis has been transformed by the use of immunomodulation therapies . Outcome measures, as judged by patient‐reported outcomes, remain an important area for development and are relevant for care delivery design .…”

mentioning

confidence: 99%

“…Outcome measures, as judged by patient‐reported outcomes, remain an important area for development and are relevant for care delivery design . The use of biomarkers that reflect natural history and response to treatment is invaluable and the use of cerebrospinal fluid neurofilament light protein and tau to correlate with brain atrophy is helpful . A provisional retrospective analysis has suggested that immunomodulatory therapy may not need to be continued indefinitely, but this needs to be the subject of further study .…”

mentioning

confidence: 99%