DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis

2014 ◽  
Vol 462 (3) ◽  
pp. 489-497 ◽  
Author(s):  
Jun Ma ◽  
Rong Wu ◽  
Qiang Zhang ◽  
Jun-bing Wu ◽  
Jizhong Lou ◽  
...  

We show that DJ-1 interacts with RACK1 and increases the dimerization and protein stability of RACK1. DJ-1 and RACK1 together protect neurons from oxidative-stress-induced apoptosis. The protein levels of DJ-1 and RACK1 decline in Parkinson's disease models.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Thuong Manh Le ◽  
Koji Hashida ◽  
Hieu Minh Ta ◽  
Mika Takarada-Iemata ◽  
Koichi Kokame ◽  
...  

Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments usingHerpud1+/+andHerpud1−/−mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes ofHerpud1−/−mice than in the astrocytes ofHerpud1+/+mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP+, an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion ofHerpud1may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.


2021 ◽  
Author(s):  
Seyed Zanyar Athari ◽  
Fereshteh Farajdokht ◽  
Saeed Sadigh Eteghad ◽  
Daryoush Mohajeri ◽  
Mir Alireza Nourazar ◽  
...  

Abstract Background: Parkinson's disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood-brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats.Methods: Wistar rats were randomly divided into sham, PD, PD+levodopa, and PD+HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo’s tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels, and α-synuclein protein expression in the SN were also measured. Results: The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. Additionally, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity.Conclusion: According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.


2020 ◽  
Vol 13 (03) ◽  
pp. 2050013
Author(s):  
Gaobin Zhang ◽  
Zheng Li ◽  
Fangjie Chen ◽  
Duoteng Zhang ◽  
Wenhui Ji ◽  
...  

Parkinson’s disease (PD) is closely related to the oxidative stress induced by excess hydrogen peroxide (H2O2) in organisms. Developing an efficient method for noninvasive and real-time H2O2 detection is beneficial to investigate the role played by H2O2 in PD. In this work, a novel fluorogenic probe (CBH) for living organisms H2O2 detection has been designed, synthesized and characterized. The emission of CBH in PBS solution is very weak. However, when H2O2 was added, the fluorescence of CBH solution was sharply increased for 12-fold, accompanied by the emission peak blue-shifted from 600 to 530 nm. Moreover, the response of CBH to H2O2 is highly sensitive and selective and is not affected by various ROS/RNS, anions, cations, and amino acids. Based on the good performance of CBH for H2O2 detection, it has been successfully applied to visualizing the H2O2 concentration in living cells, Zebrafish and [Formula: see text]. elegans PD models.


2012 ◽  
Vol 11 (4) ◽  
pp. 430-438 ◽  
Author(s):  
Marcella Reale ◽  
Mirko Pesce ◽  
Medha Priyadarshini ◽  
Mohammad A Kamal ◽  
Antonia Patruno

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