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Orexin pathway in Parkinson’s disease: a review

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease (NDD) caused by dopaminergic neuron degeneration in the substantia nigra (SN). Orexin is a neuropeptide that plays a role in the pathogenesis of PD. Orexin has neuroprotective properties in dopaminergic neurons. In PD neuropathology, there is also degeneration of orexinergic neurons in the hypothalamus, in addition to dopaminergic neurons. However, the loss of orexinergic neurons in PD began after the degeneration of dopaminergic neurons. Reduced activity of orexinergic neurons has been linked to developing and progressing motor and non-motor symptoms in PD. In addition, the dysregulation of the orexin pathway is linked to the development of sleep disorders. The hypothalamic orexin pathway regulates various aspects of PD neuropathology at the cellular, subcellular, and molecular levels. Finally, non-motor symptoms, particularly insomnia and disturbed sleep, promote neuroinflammation and the accumulation of neurotoxic proteins as a result of defects in autophagy, endoplasmic reticulum (ER) stress, and the glymphatic system. As a result, this review aimed to highlight the potential role of orexin in PD neuropathology.

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Acknowledgements

The authors would like to thank the Deanship of Scientific Research at Shaqra University for supporting this work.

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Authors and Affiliations

  1. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, 11961, Saudi Arabia

    Mohammed Alrouji

  2. Department of clinical pharmacology and therapeutic medicine, college of medicine, Mustansiriyah University, Baghdad, Iraq

    Hayder M. Al-Kuraishy & Ali I. Al-Gareeb

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt

    Dalia Zaafar

  4. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Al Beheira, Egypt

    Gaber El-Saber Batiha

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H.M.A., A.I.A., D.Z., and G.E.B. reviewed the literature and wrote the first draft of the manuscript. M.A., H.M.A., A.I.A., D.Z., and G.E.B. revised and edited the manuscript. A.I.A and D.Z conceptualized and determined the scope of the manuscript and had primary responsibility for the final content. M.A., H.M.A. and G.E.B. supervised the review process. All authors meet ICMJE criteria for authorship and approve the final version for publication.

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Alrouji, M., Al-Kuraishy, H.M., Al-Gareeb, A.I. et al. Orexin pathway in Parkinson’s disease: a review. Mol Biol Rep 50, 6107–6120 (2023). https://doi.org/10.1007/s11033-023-08459-5

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  • DOI: https://doi.org/10.1007/s11033-023-08459-5

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