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Review
. 2024 Aug 24;25(17):9197.
doi: 10.3390/ijms25179197.

The Role of α-Synuclein in Etiology of Neurodegenerative Diseases

Daria Krawczuk  1 , Magdalena Groblewska  2 , Jan Mroczko  1 , Izabela Winkel  3 , Barbara Mroczko  1   2
Affiliations
Review

The Role of α-Synuclein in Etiology of Neurodegenerative Diseases

Daria Krawczuk et al. Int J Mol Sci. .

Abstract

A presynaptic protein called α-synuclein plays a crucial role in synaptic function and neurotransmitter release. However, its misfolding and aggregation have been implicated in a variety of neurodegenerative diseases, particularly Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Emerging evidence suggests that α-synuclein interacts with various cellular pathways, including mitochondrial dysfunction, oxidative stress, and neuroinflammation, which contributes to neuronal cell death. Moreover, α-synuclein has been involved in the propagation of neurodegenerative processes through prion-like mechanisms, where misfolded proteins induce similar conformational changes in neighboring neurons. Understanding the multifaced roles of α-synuclein in neurodegeneration not only aids in acquiring more knowledge about the pathophysiology of these diseases but also highlights potential biomarkers and therapeutic targets for intervention in alpha-synucleinopathies. In this review, we provide a summary of the mechanisms by which α-synuclein contributes to neurodegenerative processes, focusing on its misfolding, oligomerization, and the formation of insoluble fibrils that form characteristic Lewy bodies. Furthermore, we compare the potential value of α-synuclein species in diagnosing and differentiating selected neurodegenerative diseases.

Keywords: Parkinson’s disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration; synucleinopathies; α-synuclein.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Structure of α-synuclein.
Figure 2
Figure 2
Biological functions of α-synuclein.
Figure 3
Figure 3
Formation of α-Syn oligomers and fibrils.
See this image and copyright information in PMC

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