IMR Press / FBL / Volume 28 / Issue 2 / DOI: 10.31083/j.fbl2802033
Open Access Review
Pathological Pathways and Alpha-Synuclein in Parkinson's Disease: A View from the Periphery
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1 Department of Biosciences, Università degli Studi di Milano, 20133 Milan, Italy
2 Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Spain
3 Fondazione Grigioni per il Morbo di Parkinson, 20125 Milan, Italy
4 Center of Excellence of Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milan, Italy
*Correspondence: (Graziella Cappelletti); (Samanta Mazzetti)
These authors contributed equally.
§ These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(2), 33;
Submitted: 20 December 2022 | Revised: 3 February 2023 | Accepted: 15 February 2023 | Published: 23 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Alpha-synuclein inclusions are the distinctive trait of brain areas affected by neurodegeneration in Parkinson’s disease (PD). Nevertheless, PD is now considered as a multisystemic disorder, since alpha-synuclein pathology has been described also outside the central nervous system. In this regard, the early, non-motor autonomic symptoms point out an important role for the peripheral nervous system during disease progression. On this basis, we propose a review of the alpha-synuclein-related pathological processes observed at peripheral level in PD, starting from molecular mechanisms, through cellular processes to systemic modifications. We discuss their relevance in the etiopathogenesis of the disease, suggesting they are concurrent players in the development of PD, and that the periphery is an easily-accessible window to look at what is occurring in the central nervous system.

860070/Innovation Programme H2020-MSCAITN-2019-EJD-Grant agreement
Fig. 1.
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