The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review
Abstract
:1. Introduction
2. Astrocytic Processes in Parkinson’s Disease
3. Alpha-Synuclein
Alpha-Syn: Its Prion-like Spreading and Presence in the Peripheral and Enteric Nervous System
4. Astrocytes and α-Syn
5. New Therapies Targeting Astrocytes and α-Syn for PD Treatment
5.1. Pharmacotherapy Targeting Astrocytes in PD
5.2. Conversion of Astrocytes to Dopaminergic Neurons and Therapies with Functional Astrocytes
5.3. Immunological Biotherapies Targeting α-Syn
5.3.1. Small-Molecule Compounds
5.3.2. Antibodies Targeting α-Syn
6. Conclusions and Future Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Therapies Targeting Astrocytes | ||||
Therapies | Effects in Astrocytes | Findings in the PD | Experimental Approach | References |
Pharmacological Rotigotine | Increased astrocyte proliferation through the overexpression of the Nrf2 signaling pathway. | Reduction in dopaminergic neurodegeneration. | α-syn transgenic mutant mice (A53T). | [108,109,110] |
NLY01 | Regulation of inflammatory signaling mediated by NF-ΚB. | Modulation of mitochondrial biogenesis and microglial inflammation, as well as enhanced autophagy. | Parkinsonian mice. | [103] |
Conversion of astrocytes into DA neurons | Reprogramming of striatal and VM astrocytes into DA neurons. | Increase in neuronal maturity, increase in levels of specific VM markers, greater resistance to cytokines, improvement of motor deficits, and restoration of DA levels in VM. | Culture of human astrocytes, PD mice 6-OHDA. | [122,123,124] |
Transplant of VM astrocytes | Grafting VM cultured astrocytes into the SNpc. | Nigrostriatal neuronal rescue, greater DA capture, improvement of motor deficits, elimination of toxic α-syn aggregates, and decrease in DA neurodegeneration. | Aged Parkinsonian mice and mice with hemi-Parkinson’s. | [123,125,126] |
Therapies Targeting α-Syn | ||||
Therapies | Effects in α-syn | Findings in the PD | Experimental Approach | References |
Natural small-molecule compounds | Suppression of neurotoxicity of α-syn oligomers, blocking of α-syn aggregation processes, and prevention of the formation of α-syn oligomers. | Reduction in motor deficits and neuroprotective effects, and a significant reduction in toxic α-syn fibrils. | Parkinsonian mice in vitro. | [128,129,130] |
α-syn-specific antibodies | Neutralization of toxic α-syn aggregates, reduced intracellular aggregation, and decreased accumulation of toxic α-syn oligomers. | Deceleration of neurodegeneration and reduction in motor deficits. | PD transgenic mice, PD mice. | [133,134,135] |
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Brash-Arias, D.; García, L.I.; Pérez-Estudillo, C.A.; Rojas-Durán, F.; Aranda-Abreu, G.E.; Herrera-Covarrubias, D.; Chi-Castañeda, D. The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review. NeuroSci 2024, 5, 71-86. https://doi.org/10.3390/neurosci5010005
Brash-Arias D, García LI, Pérez-Estudillo CA, Rojas-Durán F, Aranda-Abreu GE, Herrera-Covarrubias D, Chi-Castañeda D. The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review. NeuroSci. 2024; 5(1):71-86. https://doi.org/10.3390/neurosci5010005
Chicago/Turabian StyleBrash-Arias, David, Luis I. García, César Antonio Pérez-Estudillo, Fausto Rojas-Durán, Gonzalo Emiliano Aranda-Abreu, Deissy Herrera-Covarrubias, and Donaji Chi-Castañeda. 2024. "The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review" NeuroSci 5, no. 1: 71-86. https://doi.org/10.3390/neurosci5010005
APA StyleBrash-Arias, D., García, L. I., Pérez-Estudillo, C. A., Rojas-Durán, F., Aranda-Abreu, G. E., Herrera-Covarrubias, D., & Chi-Castañeda, D. (2024). The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review. NeuroSci, 5(1), 71-86. https://doi.org/10.3390/neurosci5010005