Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.
Keywords: Parkinson’s disease, transcellular alpha-synuclein transport, pathology progression, neurogenesis, cell replacement strategies, stem cells, induced Pluripotent Stem Cells (iPS), neurodegenerative disorder, substantia nigra, extrapiramidal system
CNS & Neurological Disorders - Drug Targets
Title:Implications of Parkinson’s Disease Pathophysiology for the Development of Cell Replacement Strategies and Drug Discovery in Neurodegenerative Diseases
Volume: 11 Issue: 7
Author(s): Francisco Pan-Montojo and Richard H.W. Funk
Affiliation:
Keywords: Parkinson’s disease, transcellular alpha-synuclein transport, pathology progression, neurogenesis, cell replacement strategies, stem cells, induced Pluripotent Stem Cells (iPS), neurodegenerative disorder, substantia nigra, extrapiramidal system
Abstract: Parkinson’s disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.
Export Options
About this article
Cite this article as:
Pan-Montojo Francisco and H.W. Funk Richard, Implications of Parkinson’s Disease Pathophysiology for the Development of Cell Replacement Strategies and Drug Discovery in Neurodegenerative Diseases, CNS & Neurological Disorders - Drug Targets 2012; 11 (7) . https://dx.doi.org/10.2174/1871527311201070907
DOI https://dx.doi.org/10.2174/1871527311201070907 |
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
-
Drug Therapies in the Secondary Prevention of Cardiovascular Diseases:Successes, Shortcomings and Future Directions
Current Vascular Pharmacology Ventilation During Pediatric CPR
Current Pediatric Reviews Patent Selections
Recent Patents on Cardiovascular Drug Discovery Opportunities for Pharmacotherapy at the Intersection of Metabolic Syndrome and Hemostasis
Current Pharmaceutical Biotechnology Human Tissue Kallikrein: A New Bullet for the Treatment of Ischemia
Current Pharmaceutical Design Non Peptidic Urotensin II Antagonists: Perspectives for a New Class of Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Analysis of the Clinical Diagnostic Value of GMFB in Cerebral Infarction
Current Pharmaceutical Biotechnology Cannabinoid Receptor Type 2 Activation in Atherosclerosis and Acute Cardiovascular Diseases
Current Medicinal Chemistry Anti-Inflammatory Effects of C-Peptide Prevent Endothelial Dysfunction in Type 1 Diabetes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) An Update on “Selenium Containing Compounds from Poison to Drug Candidates: A Review on the GPx-like Activity”
Current Chemical Biology Energy Provisioning and Inflammasome Activation: The Pivotal Role of AMPK in Sterile Inflammation and Associated Metabolic Disorders
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Exosomes: Natural Carriers for siRNA Delivery
Current Pharmaceutical Design Renin Angiotensin System as a Regulator of Cell Volume. Implications to Myocardial Ischemia
Current Cardiology Reviews Targeting Nitrosative Stress for Neurovascular Protection: New Implications in Brain Diseases
Current Drug Targets Small Molecule Inhibitors of Phosphoinositide 3-Kinase (PI3K) δ and γ
Current Topics in Medicinal Chemistry Chemokine Contribution in Stem Cell Engraftment into the Infarcted Myocardium
Current Stem Cell Research & Therapy PACAP and Its Receptors Exert Pleiotropic Effects in The Nervous System by Activating Multiple Signaling Pathways
Current Protein & Peptide Science Inhibitors of the Sphingosine Kinase Pathway as Potential Therapeutics
Current Cancer Drug Targets Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?
Current Pharmaceutical Design Intracellular Drug Delivery: Mechanisms for Cell Entry
Current Pharmaceutical Design