Abstract
Nurr1 is a member of the nuclear receptor superfamily and is a potential susceptibility gene for Parkinson’s disease (PD). Several lines of studies in vitro and in vivo reported that defects in the Nurr1 gene cause nigrostriatal neuronal deficiency as seen in PD. In the present study, we used a a synthetic low molecular weight Nurr1 activator which increases the transcription of Nurr1 to investigate whether it has anti-parkinsonian effects against nigrostriatal neuronal degeneration induced by proteasome inhibitor lactacystin. Adult C57BL/6 mice were treated orally with the Nurr1 activator and an inactive structural analog as a control at a dose of 10mg/kg per day, starting 3 days before microinjection of proteasome inhibitor lactacystin into the medial forebrain bundle and the treatment continued for a total of 4 weeks. Animal behavior tests, and pathological and biochemical examinations were performed to determine the anti-parkinsonian effects of the Nurr1 activator. We found that treatment with the Nurr1 activator significantly improved rotarod performance, attenuated dopamine neuron loss and nigrostriatal dopamine reduction, increased expression of Nurr1, dopamine transporter and vesicular monoamine transporter 2, and alleviated microglial activation in the substantia nigra of lactacystin-lesioned mice. These results suggest that the Nurr1 activator may become an innovative strategy for the treatment of PD.
Keywords: Lactacystin; Inflammation; Neuroprotection; Nurr1 gene activator; Parkinson’s disease; ubiquitin-proteasome system, Dopamine, Dopamine transporter, 4-dihydroxy-phenylacetic acid, RT-PCR,
CNS & Neurological Disorders - Drug Targets
Title:Anti-Parkinsonian Effects of Nurr1 Activator in Ubiquitin-Proteasome System Impairment Induced Animal Model of Parkinson’s Disease
Volume: 11 Issue: 6
Author(s): Zhen Zhang, Xuping Li, Wen-jie Xie, Houzhen Tuo, Samuel Hintermann, Joseph Jankovic and Weidong Le
Affiliation:
Keywords: Lactacystin; Inflammation; Neuroprotection; Nurr1 gene activator; Parkinson’s disease; ubiquitin-proteasome system, Dopamine, Dopamine transporter, 4-dihydroxy-phenylacetic acid, RT-PCR,
Abstract: Nurr1 is a member of the nuclear receptor superfamily and is a potential susceptibility gene for Parkinson’s disease (PD). Several lines of studies in vitro and in vivo reported that defects in the Nurr1 gene cause nigrostriatal neuronal deficiency as seen in PD. In the present study, we used a a synthetic low molecular weight Nurr1 activator which increases the transcription of Nurr1 to investigate whether it has anti-parkinsonian effects against nigrostriatal neuronal degeneration induced by proteasome inhibitor lactacystin. Adult C57BL/6 mice were treated orally with the Nurr1 activator and an inactive structural analog as a control at a dose of 10mg/kg per day, starting 3 days before microinjection of proteasome inhibitor lactacystin into the medial forebrain bundle and the treatment continued for a total of 4 weeks. Animal behavior tests, and pathological and biochemical examinations were performed to determine the anti-parkinsonian effects of the Nurr1 activator. We found that treatment with the Nurr1 activator significantly improved rotarod performance, attenuated dopamine neuron loss and nigrostriatal dopamine reduction, increased expression of Nurr1, dopamine transporter and vesicular monoamine transporter 2, and alleviated microglial activation in the substantia nigra of lactacystin-lesioned mice. These results suggest that the Nurr1 activator may become an innovative strategy for the treatment of PD.
Export Options
About this article
Cite this article as:
Zhang Zhen, Li Xuping, Xie Wen-jie, Tuo Houzhen, Hintermann Samuel, Jankovic Joseph and Le Weidong, Anti-Parkinsonian Effects of Nurr1 Activator in Ubiquitin-Proteasome System Impairment Induced Animal Model of Parkinson’s Disease, CNS & Neurological Disorders - Drug Targets 2012; 11 (6) . https://dx.doi.org/10.2174/187152712803581155
DOI https://dx.doi.org/10.2174/187152712803581155 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The HIV-1 Capsid Protein as a Drug Target: Recent Advances and Future Prospects
Current Protein & Peptide Science Neurovascular Changes in Acute, sub-Acute and Chronic Mouse Models of Parkinson’s Disease
Current Neurovascular Research Oligomers on the Brain: the Emerging Role of Soluble Protein Aggregates in Neurodegeneration.
Protein & Peptide Letters Diagnostic Properties and Significance of Tongue in Persian Medicine and Chinese Medicine
Current Traditional Medicine Sphingolipid Signaling and Hematopoietic Malignancies: To the Rheostat and Beyond
Anti-Cancer Agents in Medicinal Chemistry Angiogenesis and Metastasis Inhibitors for the Treatment of Malignant Melanoma
Mini-Reviews in Medicinal Chemistry Stable Angina Pectoris: Current Medical Treatment
Current Pharmaceutical Design Oxidative Biotransformation of Fatty Acids by Cytochromes P450: Predicted Key Structural Elements Orchestrating Substrate Specificity, Regioselectivity and Catalytic Efficiency
Current Drug Metabolism Computational and Synthetic Target-based Approaches to the Discovery of Novel Anticonvulsant Compounds
Current Medicinal Chemistry Extrahepatic Metabolism may Complicate the IVIVC in Rats
Drug Metabolism Letters Current Limitations in the Treatment of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Future Perspective of Polymeric Carriers
Current Medicinal Chemistry Consequences of Alcohol Consumption on Neurotransmitters -An Overview
Current Neurovascular Research HIV-1 RT Nonnucleoside Inhibitors and Their Interaction with RT for Antiviral Drug Development
Infectious Disorders - Drug Targets Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets
Current Pharmaceutical Design Structural Bioinformatics: Methods, Concepts and Applications to Blood Coagulation Proteins
Current Protein & Peptide Science Raloxifene: Cardiovascular Considerations
Mini-Reviews in Medicinal Chemistry New Direct and Frontal Tissue Acquisition Tools for Gene Expression Analysis in Personalized Medicine
Current Pharmacogenomics and Personalized Medicine REM Sleep Behavior Disorder and Narcolepsy
CNS & Neurological Disorders - Drug Targets Endocannabinoid System: A Multi-Facet Therapeutic Target
Current Clinical Pharmacology Alzheimer Disease and Diabetes Mellitus: Do They have Anything in Common?
Current Alzheimer Research