Abstract
Previously published data from our laboratory demonstrated that pharmacological inhibition of a family of enzymes known as prolyl hydroxylase domain proteins prevents neurotoxicity associated with the acute 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine intoxication model of Parkinson’s disease in young animals. In this study, we assessed whether prolyl hydroxylase domain inhibition was neuroprotective in an inducible genetic dopaminergic glutathione depletion model previously characterized by our laboratory that more closely recapitulates the age-related and progressive nature of the human disease. Pharmacological prolyl hydroxylase domain inhibition via 3,4-dihydroxybenzoate was found to significantly attenuate hallmark mitochondrial dysfunction and loss of dopaminergic substantia nigral pars compacta neurons associated with this model. These studies further validate the possibility that prolyl hydroxylase domain inhibition may constitute a viable therapy for Parkinson’s disease.
Keywords: Drug therapy, mitochondrial function, nigrostriatal cell loss, Parkinson’s disease, prolyl hydroxylase domain proteins, transgenic mouse model, age, progressive, chronic.
CNS & Neurological Disorders - Drug Targets
Title:Pharmacological Prolyl Hydroxylase Domain Inhibition as a Therapeutic Target for Parkinson’s Disease
Volume: 13 Issue: 1
Author(s): Subramanian Rajagopalan, Shankar J. Chinta and Julie K. Andersen
Affiliation:
Keywords: Drug therapy, mitochondrial function, nigrostriatal cell loss, Parkinson’s disease, prolyl hydroxylase domain proteins, transgenic mouse model, age, progressive, chronic.
Abstract: Previously published data from our laboratory demonstrated that pharmacological inhibition of a family of enzymes known as prolyl hydroxylase domain proteins prevents neurotoxicity associated with the acute 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine intoxication model of Parkinson’s disease in young animals. In this study, we assessed whether prolyl hydroxylase domain inhibition was neuroprotective in an inducible genetic dopaminergic glutathione depletion model previously characterized by our laboratory that more closely recapitulates the age-related and progressive nature of the human disease. Pharmacological prolyl hydroxylase domain inhibition via 3,4-dihydroxybenzoate was found to significantly attenuate hallmark mitochondrial dysfunction and loss of dopaminergic substantia nigral pars compacta neurons associated with this model. These studies further validate the possibility that prolyl hydroxylase domain inhibition may constitute a viable therapy for Parkinson’s disease.
Export Options
About this article
Cite this article as:
Rajagopalan Subramanian, Chinta J. Shankar and Andersen K. Julie, Pharmacological Prolyl Hydroxylase Domain Inhibition as a Therapeutic Target for Parkinson’s Disease, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113126660131
DOI https://dx.doi.org/10.2174/18715273113126660131 |
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
-
Perivascular Inflammation and Hypertensive Cardiovascular Remodeling
Current Hypertension Reviews Antioxidants in Peripheral Arterial Disease
Current Drug Targets - Cardiovascular & Hematological Disorders Angiogenesis and AngiomiRs in Non-Hodgkin´s Lymphomas
Current Angiogenesis (Discontinued) Phenylbutyric Acid Protects Against Spatial Memory Deficits in a Model of Repeated Electroconvulsive Therapy
Current Neurovascular Research Infection, Infectious Agents and Vascular Disease
Reviews on Recent Clinical Trials Pleural Involvement in Systemic Disorders
Current Drug Targets - Inflammation & Allergy The Use of Colchicine in Respiratory Diseases
Current Respiratory Medicine Reviews Applications of FDG-PET/CT in Assessment of Vascular Infection and Inflammation
Current Molecular Imaging (Discontinued) Cognitive Impairment in Systemic Lupus Erythematosus: Prevalence and Clinical Importance
Current Rheumatology Reviews Effect of Leptin on Vascular Nitric Oxide and Endothelial Function
Current Hypertension Reviews The Blood-Brain Barrier: Its Influence in the Treatment of Brain Tumors Metastases
Current Cancer Drug Targets Cannabinoids and Myocardial Ischemia: Novel insights, Updated Mechanisms, and Implications for Myocardial Infarction
Current Medicinal Chemistry Perivascular Adipose Tissue, Inflammation and Vascular Dysfunction in Obesity
Current Vascular Pharmacology Matrix Metalloproteinases as Potential Targets in the Venous Dilation Associated with Varicose Veins
Current Drug Targets Blood Coagulation as an Intrinsic Pathway for Proinflammation: A Mini Review
Inflammation & Allergy - Drug Targets (Discontinued) Oxidative Stress: Meeting Multiple Targets in Pathogenesis of Vascular Endothelial Dysfunction
Current Drug Targets Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases
Current Signal Transduction Therapy Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario
Current Topics in Medicinal Chemistry A Pictorial Review of Intracranial Haemorrhage Revisited
Current Medical Imaging Effects of Highly Active Antiretroviral Therapy on Albuminuria in HIV-infected Persons
Infectious Disorders - Drug Targets