Clioquinol improves motor and non-motor deficits in MPTP-induced monkey model of Parkinson’s disease through AKT/mTOR pathway
Open Access
- 18 May 2020
- journal article
- research article
- Published by Impact Journals, LLC in Aging
- Vol. 12 (10), 9515-9533
- https://doi.org/10.18632/aging.103225
Abstract
Despite decades of research into the pathology mechanisms of Parkinson's disease (PD), disease-modifying therapy of PD is scarce. Thus, searching for new drugs or more effective neurosurgical treatments has elicited much interest. Clioquinol (CQ) has been shown to have therapeutic benefits in rodent models of neurodegenerative disorders. However, it's neuroprotective role and mechanisms in PD primate models and PD patients, especially in the advanced stages, are not fully understood. Furthermore, issues such as spontaneous recovery of motor function and high symptom variability in different monkeys after the same toxic protocol, has not been resolved before the present study. In this study, we designed a chronic and long-term progressive protocol to generate a stabilized PD monkey model showed with classic motor and non-motor deficits, followed by treatment analysis of CQ. We found that CQ could remarkably improve the motor and non-motor deficits, which were based on the reduction of iron content and ROS level in the SN and further improvement in pathology. Meanwhile, we also showed that ferroptosis was probably involved in the pathogenesis of PD. In addition, the study shows a positive effect of CQ on AKT/mTOR survival pathway and a blocking effect on p53 medicated cell death in vivo and in vitro.Keywords
This publication has 71 references indexed in Scilit:
- A critique of available scales and presentation of the non‐human primate dyskinesia rating scaleMovement Disorders, 2012
- Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell DeathCell, 2012
- Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signalingJCI Insight, 2012
- Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron lossNature Neuroscience, 2009
- PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell DeathMolecular Cell, 2009
- Current approaches to the treatment of Parkinson’s diseaseNeuropsychiatric Disease and Treatment, 2008
- Small-molecule aggregates inhibit amyloid polymerizationNature Chemical Biology, 2008
- Molecular markers of early Parkinson's disease based on gene expression in bloodProceedings of the National Academy of Sciences of the United States of America, 2007
- Oxidative stress in Parkinson's diseaseAnnals of Neurology, 2003
- AGEING AND PARKINSON'S DISEASE: SUBSTANTIA NIGRA REGIONAL SELECTIVITYBrain, 1991