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Serum fractalkine and 3-nitrotyrosine levels correlate with disease severity in Parkinson’s disease: a pilot study

Abstract

Parkinson’s disease (PD) and Parkinsonian syndromes; Progressive supranuclear palsy (PSP), and Multiple system atrophy (MSA) are debilitating neurodegenerative disorders. Fractalkine is a chemokine involved in neuroinflammation, whereas, 3-nitrotyrosine (3-NT) is a marker of early neurodegenerative cellular-damage. We measured Fractalkine and 3-NT levels in the serum of these patients to examine the neuroinflammation hypothesis and also to decipher the propensity of these biologics to be used as early (5 years from onset) biochemical markers in neurodegenerative Parkinsonism. The diagnoses of PD, PSP and MSA were performed as per the respective clinical criteria. 21 PD, 9 PSP and 8 MSA patients along with controls participated in this study. Serum concentrations of Fractalkine and 3-NT were measured by ELISA. Fractalkine levels were increased in PD, PSP and MSA cohorts in comparison with controls with p < 0.001, p < 0.05 and p < 0.05 respectively. Levels of 3-NT also showed elevation in PD (p < 0.01) vs. controls. However, Pearson plot showed that Fractalkine levels were high in the patients with unified Parkinson’s disease rating scale (UPDRS) part III motor score of 1, meaning slight disability, but gradually dropped in patients with motor score of 4, which is a measure of severe motor disability. This negative correlation (− .565, p < .0.01) also accentuates the neuroprotectant/anti-inflammatory nature of Fractalkine in PD. Continuous rise of 3-NT in PD, positively correlating (.512, p < 0.05) with worsening motor symptoms points to deleterious consequences of nitrosative stress. To our knowledge, this is the first report providing evidence that serum Fractalkine and 3-NT have early diagnostic/prognostic significance as PD biomarkers.

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Abbreviations

PD:

Parkinson’s disease

PSP:

Progressive supranuclear palsy

MSA:

Multiple system atrophy

3-NT:

3-Nitrotyrosine

NO:

Nitric oxide

CX3CL1:

Fractalkine

ROS:

Reactive oxygen species

ELISA:

Enzyme-linked immunosorbent assay

ALS:

Amyotrophic lateral sclerosis

AD:

Alzheimer’s disease

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Acknowledgements

This study was supported by a grant from the Council of Science and Technology (CST) (CST/SERPD/D-301), U.P. India to GNB.

Funding

The corresponding author (GNB) has received a research grant from the Council of Science and Technology, Uttar Pradesh (U.P), India for carrying out this research, which is a not-for- profit scientific organization of the state government of U.P for promoting research. VKP was a co-investigator and MG was a research assistant in the project.

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Correspondence to G. Nagesh Babu.

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Gupta, M., Paliwal, V.K. & Babu, G.N. Serum fractalkine and 3-nitrotyrosine levels correlate with disease severity in Parkinson’s disease: a pilot study. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00801-9

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Keywords

  • Parkinson’s disease
  • Progressive supranuclear palsy
  • Multiple system atrophy
  • Fractalkine
  • 3-Nitrotyrosine
  • Inflammation