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Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction
Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V.. Cell death & disease, 2023-03-01
Topic: Brain proteins, microglia and lab models
Although the discovery of the critical role of α-synuclein (α-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Calabresi, P., Mechelli, A., Natale, G., Volpicelli-Daley, L., Di Lazzaro, G., & Ghiglieri, V. (2023). Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell death & disease. https://doi.org/10.1038/s41419-023-05672-9
Vancouver
Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell death & disease. 2023. doi:10.1038/s41419-023-05672-9. PMID: 36859484.
BibTeX
@article{calabresi2023-36859484,
author = {Calabresi, P. and Mechelli, A. and Natale, G. and Volpicelli-Daley, L. and Di Lazzaro, G. and Ghiglieri, V.},
title = {{Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction}},
journal = {Cell death \& disease},
year = {2023},
doi = {10.1038/s41419-023-05672-9},
pmid = {36859484},
url = {https://doi.org/10.1038/s41419-023-05672-9}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder.
- Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest.
- In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction.
- The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn.
- In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
Why it matters
This review discusses how abnormal forms of alpha-synuclein cause neuronal death and early synaptic changes in Parkinson's disease and related disorders such as dementia with Lewy bodies. It states that understanding these early mechanisms is important for research on biomarkers and possible disease-modifying therapies targeting alpha-synuclein, but reports no treatment, cure, or prevention.
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Study details
- Evidence strengthLow
How this study scored 56/100
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 (Cell death & disease) |
| Journal's citation record | 2 / 4 | Cell Death and Disease: journal h-index 233 (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 | 3 / 5 | 2023 — within 6 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 818 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 163.6 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 6 / 6 | Cited 120.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 4 / 4 | Cited 772 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Veronica Ghiglieri: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Alabama at Birmingham: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36859484) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
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Read the original
- DOI: 10.1038/s41419-023-05672-9
- PubMed: 36859484
- Original source →
- Free full text: Cell Death and Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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