Soluble LAG-3 and Toll-interacting protein: Novel upstream neuro-inflammatory markers in Parkinson's disease

Roy, Akash; Choudhury, Supriyo; Banerjee, Rebecca; Basu, Purba; Kumar, Hrishikesh

doi:10.1016/j.parkreldis.2021.09.019

Cited by 11 publications

(8 citation statements)

References 7 publications

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“…Since the previously commented data suggest that LAG3 could be a reliable marker for PD, 7 , 8 , 9 it seems reasonable to address the possible association between the most relevant polymorphisms in the LAG3 gene and in its closely related CD4 gene with the risk of developing PD.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, another study did not find expression of LAG3 in human and murine neurons and did not find that overexpression of LAG3 in cultured human neural cells caused worsening of α‐syn pathology, and did not confirm changes in survival in α‐syn transgenic mice by LAG3 depletion 6 . Serum soluble LAG3 levels are significantly increased in PD patients compared with controls in two studies 7,8 . Another study showed similar serum soluble LAG3 levels but increased CSF‐soluble LAG3 concentrations in PD patients compared with controls 9 .…”

Section: Introductionmentioning

confidence: 96%

“…6 Serum soluble LAG3 levels are significantly increased in PD patients compared with controls in two studies. 7,8 Another study showed similar serum soluble LAG3 levels but increased CSF-soluble LAG3 concentrations in PD patients compared with controls. 9 These data suggest that LAG3 could be a potential biomarker for PD, and its genetic variability can be related to the risk of presenting PD.…”

Section: Introductionmentioning

confidence: 99%

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Association between LAG3/CD4 gene variants and risk of Parkinson's disease

García‐Martín

Pástor

Gómez-Tabales

et al. 2022

Eur J Clin Investigation

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Background/Objectives Several recent studies suggest a possible role of lymphocyte activation 3 (LAG3) protein. LAG3 can behave as an α‐synuclein ligand, and serum and cerebrospinal fluid‐soluble LAG3 levels have been proposed as a marker of Parkinson's disease (PD). In this study, we aimed to investigate whether there is an association between 3 common single‐nucleotide variations (SNVs) in the LAG3 gene and its closely related CD4 molecule gene and the risk of PD in a Caucasian Spanish population. Two of them have been previously associated with the risk of PD in Chinese females. Methods We analysed genotypes and allele frequencies for CD4 rs1922452, CD4 951818 and LAG3 rs870849 SNVs, by using specifically designed TaqMan assays, in a cohort composed of 629 PD patients and 865 age‐ and gender‐matched healthy controls. Results The frequencies of the CD4 rs1922452 A/A genotype, according to the dominant and recessive genetic models, and of the CD4 rs1922452/A allelic variant were significantly lower, and the frequencies of the CD4 rs951818 A/A genotype, according to the dominant genetic model, and of the CD4 rs951818/A allele, were significantly higher in PD patients than in controls. The differences were not significant after stratifying by sex. These two SNVs showed strong linkage. Regression models showed a lack of relation between the 3 SNVs studied and the age at onset of PD. Conclusions These data suggest a possible role of CD4 rs1922452 and CD4 rs951818 polymorphisms in the risk of PD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Association between LAG3/CD4 gene variants and risk of Parkinson's disease

García‐Martín

Pástor

Gómez-Tabales

et al. 2022

Eur J Clin Investigation

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“…4 Our earlier work suggested that alpha synuclein-NLRP3mediated inflammation may underlie PD pathophysiology and serves as a novel therapeutic target in PD. [5][6][7] Further, we identified a significant decrease in reduced glutathione (GSH), IL-10 and brain-derived neurotrophic factor (BDNF) levels with PD severity which was reverse for pro-inflammatory cytokines and superoxide dismutase-1 (SOD1) enzyme activity. 8 Levodopa, the chemical precursor of dopamine, contributes to free radical formation and might exacerbate antioxidant dysfunction in PD.…”

Section: Introductionmentioning

confidence: 96%

Levodopa-induced Dyskinesia in Parkinson’s Disease: Plausible Inflammatory and Oxidative Stress Biomarkers

Sarkar

Roy

Choudhury

et al. 2023

Can. J. Neurol. Sci.

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Background: Pathophysiology of levodopa-induced dyskinesia (LID) remains obscure. Increased dopamine metabolism due to prolonged levodopa treatment can exacerbate oxidative damage and neuroinflammatory pathology in Parkinson’s disease (PD). Association of novel peripheral markers with LID severity might provide insight into LID pathomechanisms. Objective: We aimed to study specific peripheral blood inflammatory-oxidative markers in LID patients and investigate their association with clinical severity of LID. Method: Motor, non-motor and cognitive changes in PD with and without LID compared to healthy-matched controls were identified. Within the same cohort, inflammatory marker (sLAG3, TOLLIP, NLRP3 and IL-1β) levels and antioxidant enzyme activities were determined by ELISA and spectrophotometric methods. Results: LID patients showed distinctly upregulated TOLLIP, IL-1β levels with significant diminution of antioxidant activity compared to controls. Significant negative association of cognitive markers with oxidative changes was also observed. Conclusion: To our understanding, this is the first study that indicates the involvement of toll-like receptor-mediated distinct and low-grade inflammatory activation in LID pathophysiology.

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“…Of note, during the last few years it has been shown that different immune checkpoints can be involved in the pathogenesis of autoimmune diseases and neurodegenerative diseases, including MS, and could represent novel biomarkers, targets, or candidate genes for disease susceptibility [ 45 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis

Basile

Bramanti

Mazzon

2022

Genes

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Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.

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Soluble LAG-3 and Toll-interacting protein: Novel upstream neuro-inflammatory markers in Parkinson's disease

Cited by 11 publications

References 7 publications

Association between LAG3/CD4 gene variants and risk of Parkinson's disease

Association between LAG3/CD4 gene variants and risk of Parkinson's disease

Levodopa-induced Dyskinesia in Parkinson’s Disease: Plausible Inflammatory and Oxidative Stress Biomarkers

The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis

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