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Protective Effect of CP690550 in MPTP-Induced Parkinson’s Like Behavioural, Biochemical and Histological Alterations in Mice

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Abstract

Janus-activated kinases (JAKs) are well known to play a physiological as well as pathological role in several disease conditions such as autoimmune disorders. The present study evaluated the therapeutic potential of CP690550 (pan-JAK inhibitor) in 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) model of Parkinson’s disease. Intrastriatal administration of MPTP (30 micromol in 2 microl) produced a significant alteration in behavioural (bar test and block test). Biochemical investigations in serum and brain homogenate revealed a significant alteration in the JAK-mediated cytokine levels. MPTP administration also showed significant imbalance of inflammatory (increased TNF-α, IL-6 and NF-κb) versus anti-inflammatory cytokines (decreased IL-10 levels). MPTP-treated brain sections revealed alteration in the tissue architecture as well as undifferentiated bodies of varying contour and lesions. Chronic administration of CP690550 (3 and 10 mg/kg, po) for 7 days significantly reversed the behavioural, biochemical and histological alterations induced by MPTP. In conclusion, the findings of the present study govern the possible therapeutic potential of CP690550 in MPTP-treated mice and thus highlight the therapeutic potential of JAK inhibitors in treatment of Parkinson’s disease.

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Acknowledgements

The authors are thankful to the researchers supporting project number (RSP2022R491), King Saud University, Riyad, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia

    Abdulrahman Alshammari, Metab Alharbi, Norah A. Albekairi, Thamer H. Albekairi & Omar O. Alharbi

  2. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Pravin Yeapuri

  3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Export Promotion Industrial Park (EPIP) Zandaha Road, Dist: Vaishali, 844102, Bihar, India

    Sanjiv Singh

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  1. Abdulrahman Alshammari
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  2. Metab Alharbi
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  4. Thamer H. Albekairi
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  5. Omar O. Alharbi
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Correspondence to Sanjiv Singh.

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Alshammari, A., Alharbi, M., Albekairi, N.A. et al. Protective Effect of CP690550 in MPTP-Induced Parkinson’s Like Behavioural, Biochemical and Histological Alterations in Mice. Neurotox Res 40, 564–572 (2022). https://doi.org/10.1007/s12640-022-00498-3

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  • DOI: https://doi.org/10.1007/s12640-022-00498-3

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