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
-
Nanobiotechnology-based Drug Delivery in Brain Targeting
Current Pharmaceutical Biotechnology Editorial: (Thematic Issue: Autoimmune diseases: What have we learned from mice?)
Current Pharmaceutical Design The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias
Current Neuropharmacology Cardiovascular Effects of Green Tea Catechins: Progress and Promise
Recent Patents on Cardiovascular Drug Discovery Nitroso-Redox Balance and Modulation of Basal Myocardial Function: An Update from the Italian Society of Cardiovascular Research (SIRC)
Current Drug Targets Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges
Current Molecular Medicine Modulation of the Immune Response by Targeting Endothelial Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Editorial (Thematic Issue: From Nuisance to State-of-the-Art: FDG-PET/CT Imaging of Infection and Inflammation)
Current Molecular Imaging (Discontinued) Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature
Current Drug Targets Diversity of Human Immune System Multigene Families and its Implication in the Genetic Background of Rheumatic Diseases
Current Medicinal Chemistry Hydralazine-Induced ANCA Associated Vasculitis (AAV) Presenting with Pulmonary-Renal Syndrome (PRS): A Case Report with Literature Review
Current Cardiology Reviews MDMA Administration and Heat Shock Proteins Response: Foreseeing a Molecular Link
Current Pharmaceutical Biotechnology TNF-Alpha Antagonism in Severe Asthma?
Recent Patents on Inflammation & Allergy Drug Discovery Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View
Current HIV Research Editorial [Hot Topic:Applications of Angiotensin Converting Enzyme Inhibitors and of Angiotensin II Receptor Blockers in Pharmacology and Therapy: An Update (Executive Editor: Agostino Molteni)]
Current Pharmaceutical Design Pulmonary Manifestations of Rheumatoid Arthritis, Psoriatic Arthritis and Peripheral Spondyloarthritis: Prevalence, Diagnostic Approach and Treatment Options
Current Rheumatology Reviews Is Targeting microRNAs the Philosopher’s Stone for Vascular Disease?
Current Vascular Pharmacology Endothelial Dysfunction: Methods of Assessment and Application to Hypertension
Current Pharmaceutical Design Immunomodulation in Inflammatory Neuropathies: Rationale and Safety
Current Drug Safety Genistein: A Phytoestrogen with Multifaceted Therapeutic Properties
Mini-Reviews in Medicinal Chemistry