Advances in understanding the function of alpha-synuclein: implications for Parkinson’s disease Article Swipe
Paolo Calabresi
,
Giulia Di Lazzaro
,
Gioia Marino
,
Federica Campanelli
,
Veronica Ghiglieri
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/brain/awad150
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/brain/awad150
The critical role of alpha-synuclein in Parkinson’s disease represents a pivotal discovery. Some progress has been made over recent years in identifying disease-modifying therapies for Parkinson’s disease that target alpha-synuclein. However, these treatments have not yet shown clear efficacy in slowing the progression of this disease. Several explanations exist for this issue. The pathogenesis of Parkinson’s disease is complex and not yet fully clarified and the heterogeneity of the disease, with diverse genetic susceptibility and risk factors and different clinical courses, adds further complexity. Thus, a deep understanding of alpha-synuclein physiological and pathophysiological functions is crucial. In this review, we first describe the cellular and animal models developed over recent years to study the physiological and pathological roles of this protein, including transgenic techniques, use of viral vectors and intracerebral injections of alpha-synuclein fibrils. We then provide evidence that these tools are crucial for modelling Parkinson’s disease pathogenesis, causing protein misfolding and aggregation, synaptic dysfunction, brain plasticity impairment and cell-to-cell spreading of alpha-synuclein species. In particular, we focus on the possibility of dissecting the pre- and postsynaptic effects of alpha-synuclein in both physiological and pathological conditions. Finally, we show how vulnerability of specific neuronal cell types may facilitate systemic dysfunctions leading to multiple network alterations. These functional alterations underlie diverse motor and non-motor manifestations of Parkinson’s disease that occur before overt neurodegeneration. However, we now understand that therapeutic targeting of alpha-synuclein in Parkinson’s disease patients requires caution, since this protein exerts important physiological synaptic functions. Moreover, the interactions of alpha-synuclein with other molecules may induce synergistic detrimental effects. Thus, targeting only alpha-synuclein might not be enough. Combined therapies should be considered in the future.
Related Topics
Concepts
Alpha-synuclein
Parkinson's disease
Disease
Neuroscience
Alpha (finance)
Function (biology)
Medicine
Psychology
Biology
Pathology
Clinical psychology
Genetics
Construct validity
Psychometrics
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.1093/brain/awad150
- https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awad150/50315663/awad150.pdf
- OA Status
- hybrid
- Cited By
- 112
- References
- 90
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4376573632
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4376573632Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/brain/awad150Digital Object Identifier
- Title
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Advances in understanding the function of alpha-synuclein: implications for Parkinson’s diseaseWork title
- Type
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reviewOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-05-15Full publication date if available
- Authors
-
Paolo Calabresi, Giulia Di Lazzaro, Gioia Marino, Federica Campanelli, Veronica GhiglieriList of authors in order
- Landing page
-
https://doi.org/10.1093/brain/awad150Publisher landing page
- PDF URL
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https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awad150/50315663/awad150.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
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https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awad150/50315663/awad150.pdfDirect OA link when available
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Alpha-synuclein, Parkinson's disease, Disease, Neuroscience, Alpha (finance), Function (biology), Medicine, Psychology, Biology, Pathology, Clinical psychology, Genetics, Construct validity, PsychometricsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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112Total citation count in OpenAlex
- Citations by year (recent)
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2025: 63, 2024: 45, 2023: 3Per-year citation counts (last 5 years)
- References (count)
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90Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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