Abstract
Cell replacement therapies are an attractive mode of treatment for neurodegenerative disorders as they have the potential to alleviate or modify disease symptoms and restore function. In Parkinson’s disease, the cell type requiring replacement is dopamine-producing neurons of the midbrain. The source of replacement cells is contentious, with opinion still evolving. Clinical trials have previously used fetal brain tissue; however, this will likely be superseded by the use of embryonic or induced pluripotent stem cells, due to their greater availability and homogeneity. One significant caveat in the use of any cell source for therapy is that cells must first be adequately characterised and purified. The gold standard marker in the identification of dopaminergic neurons is tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, catalyzing the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine. However, there are multiple ways of measuring TH readout, and potential flaws in the fidelity of TH expression. This review will look at the complex regulatory mechanisms that govern different facets of TH expression, including reported differences in TH expression in vitro and in vivo. We will also examine the regulation of the TH gene; assessing the which, the where and the when of TH expression. We will look at how knowledge of regulation of the TH gene can be utilised to enhance research efforts. And, finally we will delve into the transcription factors that govern elements of TH expression, and which may prove more effective for defining appropriate dopaminergic neuron precursor cells.
Keywords: Cell replacement therapy, dopaminergic neuron, Nurr1, Parkinson’s disease, Pitx3, transcriptional regulation, Tyrosine hydroxylase.
CNS & Neurological Disorders - Drug Targets
Title:Moving Beyond Tyrosine Hydroxylase to Define Dopaminergic Neurons for Use in Cell Replacement Therapies for Parkinson’s Disease
Volume: 11 Issue: 4
Author(s): Robert B. White and Meghan G. Thomas
Affiliation:
Keywords: Cell replacement therapy, dopaminergic neuron, Nurr1, Parkinson’s disease, Pitx3, transcriptional regulation, Tyrosine hydroxylase.
Abstract: Cell replacement therapies are an attractive mode of treatment for neurodegenerative disorders as they have the potential to alleviate or modify disease symptoms and restore function. In Parkinson’s disease, the cell type requiring replacement is dopamine-producing neurons of the midbrain. The source of replacement cells is contentious, with opinion still evolving. Clinical trials have previously used fetal brain tissue; however, this will likely be superseded by the use of embryonic or induced pluripotent stem cells, due to their greater availability and homogeneity. One significant caveat in the use of any cell source for therapy is that cells must first be adequately characterised and purified. The gold standard marker in the identification of dopaminergic neurons is tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, catalyzing the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine. However, there are multiple ways of measuring TH readout, and potential flaws in the fidelity of TH expression. This review will look at the complex regulatory mechanisms that govern different facets of TH expression, including reported differences in TH expression in vitro and in vivo. We will also examine the regulation of the TH gene; assessing the which, the where and the when of TH expression. We will look at how knowledge of regulation of the TH gene can be utilised to enhance research efforts. And, finally we will delve into the transcription factors that govern elements of TH expression, and which may prove more effective for defining appropriate dopaminergic neuron precursor cells.
Export Options
About this article
Cite this article as:
B. White Robert and G. Thomas Meghan, Moving Beyond Tyrosine Hydroxylase to Define Dopaminergic Neurons for Use in Cell Replacement Therapies for Parkinson’s Disease, CNS & Neurological Disorders - Drug Targets 2012; 11 (4) . https://dx.doi.org/10.2174/187152712800792758
DOI https://dx.doi.org/10.2174/187152712800792758 |
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
-
Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry Therapeutic Implications of Superoxide Dismutase And Its Importance in Kinase Drug Discovery
Current Topics in Medicinal Chemistry Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry The MYCN Oncogene as a Specific and Selective Drug Target for Peripheral and Central Nervous System Tumors
Current Cancer Drug Targets Cell Surface Nucleolin as a Target for Anti-Cancer Therapies
Recent Patents on Anti-Cancer Drug Discovery Antitumoral Potential of Snake Venom Phospholipases A2 and Synthetic Peptides
Current Pharmaceutical Biotechnology Disintegrins from Snake Venoms and their Applications in Cancer Research and Therapy
Current Protein & Peptide Science Suicidal Inactivation of Methemoglobin by Generation of Thiyl Radical: Insight into NAC Mediated Protection in RBC
Current Molecular Medicine Ferric Cycle Activity and Alzheimer Disease
Current Neurovascular Research Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Regulators of Intracellular Calcium Release Channels
Current Pharmaceutical Design Edelfosine in Membrane Environment - the Langmuir Monolayer Studies
Anti-Cancer Agents in Medicinal Chemistry Immune Checkpoint Inhibitors: Basics and Challenges
Current Medicinal Chemistry Epigenetic and miRNAs Dysregulation in Prostate Cancer: The role of Nutraceuticals
Anti-Cancer Agents in Medicinal Chemistry In-Situ Hybridization as a Molecular Tool in Cancer Diagnosis and Treatment
Current Medicinal Chemistry Interleukin-18: Biology and Role in the Immunotherapy of Cancer
Current Medicinal Chemistry Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease
Current Alzheimer Research Intracellular Aβ and its Pathological Role in Alzheimer’s Disease: Lessons from Cellular to Animal Models
Current Alzheimer Research Sarcosine-Based Glycine Transporter Type-1 (GlyT-1) Inhibitors Containing Pyridazine Moiety: A Further Search for Drugs with Potential to Influence Schizophrenia Negative Symptoms
Current Pharmaceutical Design