The involvement of JAK/STAT signaling pathway in the treatment of Parkinson's disease

  • Naser-Aldin Lashgari
    Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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  • Nazanin Momeni Roudsari
    Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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  • Saeideh Momtaz
    Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran, Iran

    Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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  • Thozhukat Sathyapalan
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom
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  • Amir Hossein Abdolghaffari
    Correspondence to: A. H.Abdolghaffari, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
    Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran, Iran

    Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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  • Amirhossein Sahebkar
    Correspondence to: A. Sahebkar, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
    Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    School of Medicine, The University of Western Australia, Perth, Australia

    School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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      • Parkinson's disease (PD) is a neurodegenerative disorder in which inflammation plays a key role.
      • Deregulation of the JAK/STAT signaling pathway is implicated in PD pathogenesis.
      • Several cytokines, chemokines, growth factors, and hormones stimulate the JAK/STAT pathway in PD.
      • JAK/STAT pathway represents a promising target for PD therapy.
      • A variety of synthetic or natural small-molecule JAK inhibitors with therapeutic effects have been identified.


      Parkinson's disease (PD) is a neurodegenerative disorder in which inflammation and oxidative stress play key etiopathological role. The pathology of PD brain is characterized by inclusions of aggregated α-synuclein (α-SYN) in the cytoplasmic region of neurons. Clinical evidence suggests that stimulation of pro-inflammatory cytokines leads to neuroinflammation in the affected brain regions. Upon neuroinflammation, the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway, and other transcription factors such as nuclear factor κB (NF-κB), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), mammalian target of rapamycin (mTOR), and toll-like receptors (TLRs) are upregulated and induce the microglial activation, contributing to PD via dopaminergic neuron autophagy. Aberrant activation or phosphorylation of the components of JAK/STAT signaling pathway has been implicated in increased transcription of the inflammation-associated genes and many neurodegenerative disorders such as PD. Interferon gamma (IFN-γ), and interleukine (IL)-6 are two of the most potent activators of the JAK/STAT pathway, and it was shown to be elevated in PD. Stimulation of microglial cell with aggregated α-SYN results in production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and IL-1β in PD. Dysregulation of the JAK/STAT in PD and its involvement in various inflammatory pathways make it a promising PD therapy approach. So far, a variety of synthetic or natural small-molecule JAK inhibitors (Jakinibs) have been found promising in managing a spectrum of ailments, many of which are in preclinical research or clinical trials. Herein, we provided a perspective on the function of the JAK/STAT signaling pathway in PD progression and gathered data that describe the rationale evidence on the potential application of Jakinibs to improve neuroinflammation in PD.


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