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 |
- 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
-
Triggering Receptor Expressed on Myeloid Cells (TREM) Family and the Application of Its Antagonists
Recent Patents on Anti-Infective Drug Discovery Ophthalmological and Otological Manifestations in the Antiphospholipid Syndrome
Current Rheumatology Reviews Overview of Hyperuricaemia and Gout
Current Pharmaceutical Design Angiogenesis and AngiomiRs in Non-Hodgkin´s Lymphomas
Current Angiogenesis (Discontinued) Duration of Dual Antiplatelet Therapy After Coronary Stenting
Current Pharmaceutical Design Lycopene and Cardiovascular Diseases: An Update
Current Medicinal Chemistry Synthetic Approaches to the Multifunctional Drug Ebselen and Analogs: Past and Present
Mini-Reviews in Organic Chemistry Crohns Targeted Therapy: Myth or Real Goal?
Current Drug Discovery Technologies STING Activation and its Application in Immuno-Oncology
Current Topics in Medicinal Chemistry Protective Effects of Astaxanthin on Nephrotoxicity in Rats with Induced Renovascular Occlusion
Combinatorial Chemistry & High Throughput Screening Angiogenic Growth Factors in the Treatment of Peripheral Arterial Disease
Current Vascular Pharmacology Is the Vasculature a Potential Therapeutic Target in Arthritis?
Current Rheumatology Reviews Behcets Syndrome: Literature Review
Current Rheumatology Reviews Haptoglobin Phenotype Correlates with the Extent of Cerebral Deep White Matter Lesions in Hypertensive Patients
Current Neurovascular Research Clinical, Immunological and Therapeutic Aspects of Autoimmune Encephalitis
Recent Patents on CNS Drug Discovery (Discontinued) Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins
Current Topics in Medicinal Chemistry Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases
Current Pharmaceutical Design Subject Index To Volume 3
Current Neurovascular Research Leptin and Vascular Smooth Muscle Cells
Current Pharmaceutical Design Anti-VEGF Treatment in Corneal Diseases
Current Drug Targets