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<p>Multiple sclerosis is a debilitating demyelinating progressive neurodegenerative disease, that eventually leads to the death of patients. Transcriptomic patient dataset analysis revealed marked alterations in P<sub>2</sub>Y<sub>12</sub> expression in microglia from individuals with Multiple Sclerosis. Absorption, Distribution, Metabolism, and Excretion (ADME) profiling highlighted clopidogrel, a P<sub>2</sub>Y<sub>12</sub> inhibitor, as a potentially promising treatment option for advanced stages of the disease. Our previous invitro studies using N9 microglial cells showed that, clopidogrel effectively mitigated TNF-α mediated inflammatory response and chemotaxis. We employed targeted metabolomic analysis of healthy, cuprizone-fed, clopidogrel-treated, and clopidogrel-treated cuprizone-fed mice to understand the metabolic modulation associated with clopidogrel treatment. Our analysis reveals that cuprizone-fed mice show deregulation of metabolic pathways important for lipid, oxidative stress, and biotin metabolism. Notably, clopidogrel modulates metabolic pathways in cuprizone-fed mice particularly involved in lipid, biotin and myelin biosynthesis. Taken together, our earlier findings with N9 microglial cells and current results from the cuprizone-fed mice model suggest clopidogrel as a potential therapeutic agent in Multiple Sclerosis.</p>

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Clopidogrel modulate deregulated metabolic pathways in cuprizone fed mice model of Multiple Sclerosis

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Saiswaroop Rajaratnam,
  • V. M. Datta Darshan,
  • Ashwin Ashok Naik,
  • Sai Krishna Srimadh Bhagavatham,
  • Vishnu Kannan,
  • Sai Sanwid Pradhan,
  • Sriram Rathnakumar,
  • Sai Prashanth Santhapuri,
  • Brahma Naidu Parim,
  • Ahmed Mir Irfan,
  • Sudheeran Kannoth,
  • E. V. Joshy,
  • Natarajan Arumugam,
  • Abdulrahman I. Almansour,
  • Piruthivi Sukumar,
  • Vijayalakshmi Venkatesan,
  • Venketesh Sivaramakrishnan

摘要

Multiple sclerosis is a debilitating demyelinating progressive neurodegenerative disease, that eventually leads to the death of patients. Transcriptomic patient dataset analysis revealed marked alterations in P2Y12 expression in microglia from individuals with Multiple Sclerosis. Absorption, Distribution, Metabolism, and Excretion (ADME) profiling highlighted clopidogrel, a P2Y12 inhibitor, as a potentially promising treatment option for advanced stages of the disease. Our previous invitro studies using N9 microglial cells showed that, clopidogrel effectively mitigated TNF-α mediated inflammatory response and chemotaxis. We employed targeted metabolomic analysis of healthy, cuprizone-fed, clopidogrel-treated, and clopidogrel-treated cuprizone-fed mice to understand the metabolic modulation associated with clopidogrel treatment. Our analysis reveals that cuprizone-fed mice show deregulation of metabolic pathways important for lipid, oxidative stress, and biotin metabolism. Notably, clopidogrel modulates metabolic pathways in cuprizone-fed mice particularly involved in lipid, biotin and myelin biosynthesis. Taken together, our earlier findings with N9 microglial cells and current results from the cuprizone-fed mice model suggest clopidogrel as a potential therapeutic agent in Multiple Sclerosis.