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.
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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 |
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