Progress in Dopaminergic Cell Replacement and Regenerative Strategies for Parkinson's Disease
- PMID: 30346716
- DOI: 10.1021/acschemneuro.8b00389
Progress in Dopaminergic Cell Replacement and Regenerative Strategies for Parkinson's Disease
Abstract
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder symptomatically characterized by resting tremor, rigidity, bradykinesia, and gait impairment. These motor deficits suffered by PD patients primarily result from selective dysfunction or loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Most of the existing therapies for PD are based on the replacement of dopamine, which is symptomatically effective in the early stage but becomes increasingly less effective and is accompanied by serious side effects in the advanced stages of the disease. Currently, there are no strategies to slow neuronal degeneration or prevent the progression of PD. Thus, the prospect of regenerating functional dopaminergic neurons is very attractive. Over the last few decades, significant progress has been made in the development of dopaminergic regenerative strategies for curing PD. The most promising approach seems to be cell-replacement therapy (CRT) using human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), which are unlimitedly available and have gained much success in preclinical trials. Despite the challenges, stem cell-based CRT will make significant steps toward the clinic in the coming decade. Alternatively, direct lineage reprogramming, especially in situ direct conversion of glia cells to induced neurons, which exhibits some advantages including no ethical concerns, no risk of tumor formation, and even no need for transplantation, has gained much attention recently. Evoking the endogenous regeneration ability of neural stem cells (NSCs) is an idyllic method of dopaminergic neuroregeneration which remains highly controversial. Here, we review many of these advances, highlighting areas and strategies that might be particularly suited to the development of regenerative approaches that restore dopaminergic function in PD.
Keywords: Parkinson’s disease; direct lineage reprogramming; dopaminergic neurons; embryonic stem cell; endogenous regeneration; induced pluripotent stem cell; neural stem cell.
Similar articles
-
Cell therapy for Parkinson's disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts.Brain Res. 2016 May 1;1638(Pt A):15-29. doi: 10.1016/j.brainres.2015.06.054. Epub 2015 Aug 1. Brain Res. 2016. PMID: 26239914 Review.
-
Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.CNS Neurol Disord Drug Targets. 2012 Nov 1;11(7):907-20. doi: 10.2174/1871527311201070907. CNS Neurol Disord Drug Targets. 2012. PMID: 23131153 Review.
-
Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.CNS Neurol Disord Drug Targets. 2011 Jun;10(4):449-58. doi: 10.2174/187152711795563994. CNS Neurol Disord Drug Targets. 2011. PMID: 21495962 Review.
-
Replacing what's lost: a new era of stem cell therapy for Parkinson's disease.Transl Neurodegener. 2020 Jan 7;9:2. doi: 10.1186/s40035-019-0180-x. eCollection 2020. Transl Neurodegener. 2020. PMID: 31911835 Free PMC article. Review.
-
Cell-based therapies for Parkinson's disease.Expert Rev Neurother. 2011 Jun;11(6):831-44. doi: 10.1586/ern.11.33. Expert Rev Neurother. 2011. PMID: 21651331 Review.
Cited by
-
Umbilical cord blood-derived exosomes attenuate dopaminergic neuron damage of Parkinson's disease mouse model.J Nanobiotechnology. 2024 Sep 14;22(1):567. doi: 10.1186/s12951-024-02773-1. J Nanobiotechnology. 2024. PMID: 39277761 Free PMC article.
-
Revolutionizing our understanding of Parkinson's disease: Dr. Heinz Reichmann's pioneering research and future research direction.J Neural Transm (Vienna). 2024 Aug 7. doi: 10.1007/s00702-024-02812-z. Online ahead of print. J Neural Transm (Vienna). 2024. PMID: 39110245 Review.
-
Potential injectable hydrogels as biomaterials for central nervous system injury: A narrative review.Ibrain. 2023 Nov 30;9(4):402-420. doi: 10.1002/ibra.12137. eCollection 2023 Winter. Ibrain. 2023. PMID: 38680508 Free PMC article. Review.
-
Closing the loop for patients with Parkinson disease: where are we?Nat Rev Neurol. 2022 Aug;18(8):497-507. doi: 10.1038/s41582-022-00674-1. Epub 2022 Jun 9. Nat Rev Neurol. 2022. PMID: 35681103 Review.
-
Endogenous versus exogenous cell replacement for Parkinson's disease: where are we at and where are we going?Neural Regen Res. 2022 Dec;17(12):2637-2642. doi: 10.4103/1673-5374.336137. Neural Regen Res. 2022. PMID: 35662194 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous