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Modeling Parkinson's Disease With the Alpha-Synuclein Protein
Gómez-Benito M, Granado N, García-Sanz P, Michel A, Dumoulin M, Moratalla R.. Frontiers in pharmacology, 2020-04-23
Topic: Brain proteins, microglia and lab models
Alpha-synuclein (α-Syn) is a key protein involved in Parkinson's disease (PD) pathology. PD is characterized by the loss of dopaminergic neuronal cells in the substantia nigra pars compacta and the abnormal accumulation and aggregation of α-Syn in the form of Lewy bodies and Lewy neurites. More precisely, the aggregation of α-Syn is associated with the dysfunctionality and degeneration of neurons in PD. Moreover, mutations in the SNCA gene, which encodes α-Syn, cause familial forms of PD and are the basis of sporadic PD risk. Given the role of the α-Syn protein in the pathology of PD, animal models that reflect the dopaminergic neuronal loss and the widespread and progressive formation of α-Syn aggregates in different areas of the brain constitute a valuable tool. Indeed, animal models of PD are important for understanding the molecular mechanisms of the disease and might contribute to the development and validation of new therapies. In the absence of animal models that faithfully reproduce human PD, in recent years, numerous animal models of PD based on α-Syn have been generated. In this review, we summarize the main features of the α-Syn pre-formed fibrils (PFFs) model and recombinant adeno-associated virus vector (rAAV) mediated α-Syn overexpression models, providing a detailed comparative analysis of both models. Here, we discuss how each model has contributed to our understanding of PD pathology and the advantages and weakness of each of them. Significance Here, we show that injection of α-Syn PFFs and overexpression of α-Syn mediated by rAAV lead to a different pattern of PD pathology in rodents. First, α-Syn PFFs models trigger the Lewy body-like inclusions formation in brain regions directly interconnected with the injection site, suggesting that there is an inter-neuronal transmission of the α-Syn pathology. In contrast, rAAV-mediated α-Syn overexpression in the brain limits the α-Syn aggregates within the transduced neurons. Second, phosphorylated α-Syn inclusions obtained with rAAV are predominantly nuclear with a punctate appearance that becomes diffuse along the neuronal fibers, whereas α-Syn PFFs models lead to the formation of cytoplasmic aggregates of phosphorylated α-Syn reminiscent of Lewy bodies and Lewy neurites.
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APA 7th
Gómez-Benito, M., Granado, N., García-Sanz, P., Michel, A., Dumoulin, M., & Moratalla, R. (2020). Modeling Parkinson's Disease With the Alpha-Synuclein Protein. Frontiers in pharmacology. https://doi.org/10.3389/fphar.2020.00356
Vancouver
Gómez-Benito M, Granado N, García-Sanz P, Michel A, Dumoulin M, Moratalla R. Modeling Parkinson's Disease With the Alpha-Synuclein Protein. Frontiers in pharmacology. 2020. doi:10.3389/fphar.2020.00356. PMID: 32390826.
BibTeX
@article{gomezbenito2020-32390826,
author = {Gómez-Benito, M. and Granado, N. and García-Sanz, P. and Michel, A. and Dumoulin, M. and Moratalla, R.},
title = {{Modeling Parkinson's Disease With the Alpha-Synuclein Protein}},
journal = {Frontiers in pharmacology},
year = {2020},
doi = {10.3389/fphar.2020.00356},
pmid = {32390826},
url = {https://doi.org/10.3389/fphar.2020.00356}
}
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Key findings
- More precisely, the aggregation of α-Syn is associated with the dysfunctionality and degeneration of neurons in PD.
- First, α-Syn PFFs models trigger the Lewy body-like inclusions formation in brain regions directly interconnected with the injection site, suggesting that there is an inter-neuronal transmission of the α-Syn pathology.
Why it matters
This review compares two animal models of Parkinson's disease based on alpha-synuclein, including pre-formed fibrils and viral overexpression, and notes that fibrils trigger Lewy body-like inclusions in connected brain regions. It is a summary of models and does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 438 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 54.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 18.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 4 / 4 | Cited 237 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rosario Moratalla: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Consejo Superior de Investigaciones Científicas: institution h-index 1,048 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32390826) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fphar.2020.00356
- PubMed: 32390826
- Original source →
- Free full text: Frontiers in Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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