Hydroxychloroquine antiparkinsonian potential: Nurr1 modulation versus autophagy inhibition

Behavioural Brain Research
Shireen A HedyaAshraf K Bahgat

Abstract

The nuclear orphan receptor (Nurr1) has recently received a perceivable solicitude as a target for the therapeutic intervention against PD. Meanwhile, the dysregulation of autophagy, along with other processes is believed to contribute massively to PD pathophysiology. Hydroxychloroquine, a hydroxy derivative of chloroquine, is an antimalarial agent which is also used as an anti-rheumatic drug. The neuroprotective potential of hydroxychloroquine and chloroquine remained controversial until recently a study showed that chloroquine exhibited an antiparkinsonian activity through Nurr1 modulation. The aim of this work is to identify whether the less toxic derivative, hydroxychloroquine, could show a similar pattern. In rat rotenone model, hydroxychloroquine effectively boosted Nurr-1 expression, exhibited an anti-inflammatory effect as verified by hindering certain pro-inflammatory cytokines and successfully reduced GSK-3β activity. Consequently, an increase in the striatal tyrosine hydroxylase content, as well as improved locomotion and muscle coordination was shown. However, this improvement was opposed by hydroxychloroquine induced autophagic inhibition as manifested by enhancing both LC3-II and P62 levels possibly through the pr...Continue Reading

Citations

Jul 28, 2020·EMBO Molecular Medicine·Eliise Laura NirkMario Mauthe
Jan 23, 2021·Experimental & Molecular Medicine·Yongwoo JangKwang-Soo Kim
Dec 10, 2020·Cellular & Molecular Biology Letters·Liqun ChenYiyi Zhao
Aug 14, 2020·ACS Infectious Diseases·Ruiyuan CaoWu Zhong

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