Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

Version 1 : Received: 29 May 2019 / Approved: 29 May 2019 / Online: 29 May 2019 (16:37:44 CEST)

A peer-reviewed article of this Preprint also exists.

Zhang, W.; Egashira, N.; Masuda, S. Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities. Int. J. Mol. Sci. 2019, 20, 3210. Zhang, W.; Egashira, N.; Masuda, S. Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities. Int. J. Mol. Sci. 2019, 20, 3210.

Journal reference: Int. J. Mol. Sci. 2019, 20, 3210
DOI: 10.3390/ijms20133210


Although transplantation procedures have been developed for patients with end-stagec hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces depression and headache; methotrexate affects the central nervous system; mouse monoclonal immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms have greatly reduced neurotoxic events. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, using drugs to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize the recent topics on the mechanisms of neurotoxicity of immunosuppressive drugs. In addition, some information about neuroprotective effects of several immunosuppressants are also discussed.


alloimmune response; immunosuppressants; calcineurin inhibitors; corticosteroids; mTOR inhibitors; neurotoxicity; neuroprotective effects


MEDICINE & PHARMACOLOGY, Pharmacology & Toxicology

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